EP1541557A1 - Phenylpyridine compound and bactericidal composition containing the same - Google Patents
Phenylpyridine compound and bactericidal composition containing the same Download PDFInfo
- Publication number
- EP1541557A1 EP1541557A1 EP03788085A EP03788085A EP1541557A1 EP 1541557 A1 EP1541557 A1 EP 1541557A1 EP 03788085 A EP03788085 A EP 03788085A EP 03788085 A EP03788085 A EP 03788085A EP 1541557 A1 EP1541557 A1 EP 1541557A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- group
- och
- compound
- hydrogen atom
- atom
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 0 *c(cc1)ccc1-c(nccc1)c1NC(C(c(cc1)ccc1Cl)OCC#C)=O Chemical compound *c(cc1)ccc1-c(nccc1)c1NC(C(c(cc1)ccc1Cl)OCC#C)=O 0.000 description 1
- HRGVFBNGLQRGJZ-UHFFFAOYSA-N CC(C)(C=CC=C1[N+]([O-])=O)C(C)=C1Cl Chemical compound CC(C)(C=CC=C1[N+]([O-])=O)C(C)=C1Cl HRGVFBNGLQRGJZ-UHFFFAOYSA-N 0.000 description 1
- JDHOZFNYCLTLCJ-UHFFFAOYSA-N COc(cc1)ccc1-c(nccc1)c1N Chemical compound COc(cc1)ccc1-c(nccc1)c1N JDHOZFNYCLTLCJ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
Definitions
- the present invention relates a phenylpyridine compound and a fungicidal composition comprising the same.
- a phenylpyridine compound (1) represented by the following formula has an excellent controlling activity against plant diseases and accomplished the present invention.
- the present invention provides:
- the halogen atom includes a fluorine atom, a chlorine atom, a bromine atom and the like
- the C1-C6 alkyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a hexyl group and the like
- the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorodifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a trichloromethyl group, a dichlorobromomethyl group, a pent
- the C1-C3 alkyl group includes a methyl group, an ethyl group, a propyl group and the like.
- the halogen atom includes a fluorine atom, a chlorine atom, a bromine atom and the like.
- the C1-C3 alkyl group includes a methyl group, an ethyl group, a propyl group and the like.
- the halogen atom includes a fluorine atom, a chlorine atom, a bromine atom and the like
- the C1-C6 alkyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a hexyl group and the like
- the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorodifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a trichloromethyl group, a dichlorobromomethyl group, a pentafluoroethyl group, a
- the halogen atom includes a fluorine atom, a chlorine atom, a bromine atom and the like
- the C1-C3 alkyl group includes a methyl group, an ethyl group, a propyl group and the like
- the C1-C3 alkoxy group includes a methoxy group, an ethoxy group, a propoxy group and the like
- the C1-C3 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chloromethyl group, a bromomethyl group, a 2,2,2-trifluoroethyl group, a trichloromethyl group and the like.
- the C1-C3 alkyl group includes a methyl group, an ethyl group, a propyl group and the like.
- the C1-C6 alkyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a hexyl group and the like;
- the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a trichloromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2, 2,2-trifluoroethyl group, a 6, 6, 6-trifluorohexyl group and the like;
- the C3-C6 alkenyl group includes a methyl
- the C1-C6 alkyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a hexyl group and the like;
- the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, a 2, 2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6, 6, 6-trif luorohexyl group and the like;
- the C3-C6 alkenyl group includes a 2-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, a 2-buten
- the halogen atom includes a fluorine atom, a chlorine atom, a bromine atom and the like
- the C1-C6 alkyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a hexyl group and the like
- the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6,6,6-trifluoro
- the halogen atom includes a fluorine atom, a chlorine atom, a bromine atom and the like
- the C1-C6 alkyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a hexyl group and the like
- the C1-C6 haloalkyl group includes a trifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6,6,6-trifluorohexyl group and the like.
- the C1-C6 alkyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a hexyl group and the like;
- the C1-C6 haloalkyl group includes a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6,6,6-trifluorohexyl group and the like;
- the C3-C6 alkenyl group includes a 2-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 2-
- the embodiment of the compound of the present invention includes, for example, the following compounds:
- the compound of the present invention can be produced, for example, according to the following (Production Method 1) to (Production Method 12).
- protecting groups may be, if necessary, applied to protect functional groups from chemical reactions.
- Said reaction is carried out in the presence of a base and usually in a solvent.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar ratio applied to the compound (3) is usually from 0.5 to 2 moles per 1 mole of the compound (2) and that to the base is 10 moles or less.
- the reaction time is usually in the range of from 0.1 to 24 hours, and the reaction temperature is in the range of from 0 to 150 °C.
- the compound (4) can be isolated by being subjectedtopost treatment procedure exemplified below.
- Said reaction is usually carried out in a solvent.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, t-butylmethylethers and the like; aliphatic hydrocarbons such as hexane, heptane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; organic nitriles such as acetonitrile, butyronitrile and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, t-butylmethylethers and the like
- aliphatic hydrocarbons such as hexane, heptane and the like
- aromatic hydrocarbons such as toluene, xylene and
- Lawesson's reagent is usually used in the molar ratio of from 1 to 10 moles per 1 mole of the compound (5).
- the reaction time is usually in the range of from 0.5 to 24 hours, and the reaction temperature is in the range of from 30 to 150 °C.
- reaction mixture After completion of the reaction, the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (6).
- post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (6).
- the isolated compound (6) can be purified by a technique such as chromatography, recrystallization and the like.
- Said reaction is carried out in the presence of a base and usually in a solvent.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons chlorobenzene and the like; esters such as butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; and tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like.
- the molar ratio applied to the compound (8) is usually from 1 to 10 moles per 1 mole of the compound (7) and that to the base is usually from 1 to 10 moles.
- the reaction time is usually in the range of from 0.5 to 24 hours, and the reaction temperature is in the range of from 0 to 120 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (9).
- the isolated compound (9) can be purified by a technique such as chromatography, recrystallization and the like.
- Said reaction is usually carried out in a solvent.
- the reducing agent used for the reaction includes sodium borohydride or potassium borohydride.
- the solvent used for the reaction includes alcohols such as methanol, ethanol, 2-propanol and the like; ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; and water and the mixture thereof.
- alcohols such as methanol, ethanol, 2-propanol and the like
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- aliphatic hydrocarbons such as hexane, heptane, octane and the like
- aromatic hydrocarbons such as toluene, xylene and the like
- the molar ratio applied to the reducing agent is usually from 0.25 to 3 moles per 1 mole of the compound (10).
- the reaction time is usually in the range of from the instant to 24 hours, and the reaction temperature is in the range of from -20 to 100 °C.
- the reaction mixture is subjected to post treatment procedure such as, after being added with an acidic water such as aqueous saturated ammonium chloride, extracting with organic solvent, subsequently drying and concentrating the organic layer obtained, to isolate the compound (11).
- the isolated compound (11) can be purified by a technique such as chromatography, recrystallization and the like.
- the compound (12) among the compounds of the present invention can be produced by subjecting the compound (10) to reaction with organic metal compounds such as alkylmagnesium halide (Grignard reagent), alkyllithium and the like which correspond to R 14-1 ;
- organic metal compounds such as alkylmagnesium halide (Grignard reagent), alkyllithium and the like which correspond to R 14-1 ;
- R 14-1 represents a C1-C3 alkyl group
- Said reaction is usually carried out in a solvent.
- the organic metal compound corresponding to R 14-1 used in the reaction is defined by an organic metal compound in which R 14-1 is the organic group coupled with a metal element, and is illustrated by alkylmagnesium halide and alkyllithium. Specifically included are methylmagnesiumbromide, methyllithium, ethylmagnesiumchloride and ethyllithium.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; and aromatic hydrocarbons such as toluene, xylene and the like.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- aliphatic hydrocarbons such as hexane, heptane, octane and the like
- aromatic hydrocarbons such as toluene, xylene and the like.
- the molar range applied to the organic metal compound is usually from 1 to 3 moles per 1 mole of the compound (10).
- the reaction time is usually in the range of from the instant to 24 hours, and the reaction temperature is in the range of from -80 to 50 °C.
- reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (12).
- post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (12).
- the isolated compound (12) can be purified by a technique such as chromatography, recrystallization and the like.
- the compound (14) and the compound (16) among the compounds of the present invention can be produced by the following method. That is, the compound (14) can be produced by subj ecting the compound (13) to reaction with an alkylsulfonyl chloride compound (Step 6-1), and furthermore, the compound (16) can be produced by subjecting the compound (14) to reaction with the compound (15)
- R 33 represents a C1-C3 alkyl group
- Said reaction is carried out in the presence of a base and usually in a solvent.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar ratio applied to the alkylsulfonyl chloride compound is usually from 1 to 3 moles per 1 mole of the compound (13) and that to the base is usually from 1 to 10 moles.
- the reaction time is usually in the range of from 0.1 to 24 hours, and the reaction temperature is in the range of from -20 to 100 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, if necessary, after the organic layer being washed by acidic water, basic water or the like, subsequently drying and concentrating the organic layer, to isolate the compound (14).
- post treatment procedure such as extracting with organic solvent, if necessary, after the organic layer being washed by acidic water, basic water or the like, subsequently drying and concentrating the organic layer, to isolate the compound (14).
- the isolated compound (14) can be purified by a technique such as recrystallization and the like.
- Said reaction is carried out with or without the presence of a solvent with or without the presence of a base.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar ratio applied to the compound (15) is usually from 1 mole to excessive amount per 1 mole of the compound (14).
- the reaction time is usually in the range of from 0.5 to 24 hours, and the reaction temperature is in the range of from 0 to 150 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, if necessary, after the organic layer being washed by acidic water, basic water or the like, subsequently drying and concentrating the organic layer, to isolate the compound (16).
- post treatment procedure such as extracting with organic solvent, if necessary, after the organic layer being washed by acidic water, basic water or the like, subsequently drying and concentrating the organic layer, to isolate the compound (16).
- the isolated compound (16) can be purified by a technique such as recrystallization and the like.
- Said reaction is usually carried out in a solvent, and if necessary, in the presence of a base.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as butylacetate, ethylacetate and the like; alcohols such as methanol, ethanol, propanol and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethyl
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate and the like
- tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like
- nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar range applied to the base is usually from the catalytic amount to 10 moles per 1 mole of the compound (17) and that to the compound (18) or the salt thereof is usually from 1 to 10 moles.
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from 0 to 150 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, and if necessary, after the organic layer being washed by acidic water, and subsequently drying and concentrating the organic layer, to isolate the compound (19).
- the isolated compound (19) can be purified by a technique such as chromatography, recrystallization and the like.
- the compound (22) among the compounds of the present invention can be produced by subjecting the compound (20) to reaction with the compound (21): (, wherein, in the formula, L 3 represents a chlorine atom, a bromine atom and a methanesulfonyloxy group; R 15-1 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group, a C3-C6 cycloalkyl group, a (C1-C6 alkyl) carbonyl group, a (C1-C6 haloalkyl) carbonyl group, a (C1-C6 alkoxy) carbonyl group, a (C1-C6 haloalkoxy)carbonyl group, a (C3-
- Said reaction is usually carried out in a solvent with the presence of a base.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and water and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar range applied to the compound (21) is usually from 1 to 3 moles per 1 mole of the compound (20) and that to the base is usually from 1 to 3 moles.
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from 0 to 150 °C.
- reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (22).
- post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (22).
- the isolated compound (22) can be purified by a technique such as chromatography, recrystallization and the like.
- Said reaction is carried out in a solvent with the presence of a catalyst.
- the solvent used for the reaction includes alcohols such as methanol, ethanol, propanol, butanol, 2-propanoland and the like; ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; water and the mixture thereof.
- alcohols such as methanol, ethanol, propanol, butanol, 2-propanoland and the like
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- aliphatic hydrocarbons such as hexane, heptane, octane and the like
- the catalyst used for the reaction includes palladium acetate, tetrakistriphenylphosphine palladium, ⁇ 1,1'-bis(diphenylphosphino)ferrocene ⁇ dichloropalladium methylene chloride complex and bis (triphenylphosphine) palladium dichloride.
- the molar range applied to the compound (27) is usually from 1 to 5 moles per 1 mole of the compound (26) and that to the catalyst is usually from 0.001 to 0.1 moles.
- Said reaction maybe, if necessary, carried out in the presence of a base (, which includes inorganic base such as sodium acetate, potassium acetate, potassium carbonate, tripotassium phosphate, sodium bicarbonate and the like) and/or a phase-transfer catalyst (, which includes quaternary ammonium salts such as tetrabutylammonium bromide, benzyltriethylammonium bromide and the like).
- a base which includes inorganic base such as sodium acetate, potassium acetate, potassium carbonate, tripotassium phosphate, sodium bicarbonate and the like
- a phase-transfer catalyst which includes quaternary ammonium salts such as tetrabutylammonium bromide, benzyltriethylammonium bromide and the like.
- the reaction time is usually in the range of from 0.5 to 24 hours, and the reaction temperature is in the range of from 50 to 120 °C.
- the reaction mixture is subjected to post treatment procedure such as filtrating as itself, subsequently concentrating the filtrate, to isolate the compound (28).
- the isolated compound (28) can be purified by a technique such as chromatography, recrystallization and the like.
- Said reaction is usually carried out in a solvent with the presence of a base.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons chlorobenzene and the like; esters such as butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; and alkali metal hydrides such as sodium hydride and the like.
- the molar range applied to the compound (41) is usually from 1 to 3 moles per 1 mole of the compound (40) and that to the base is usually from 1 to 10 moles.
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from 0 to 150 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (42).
- the isolated compound (42) can be purified by a technique such as chromatography, recrystallization and the like.
- the compound (45) among the compounds of the present invention can be produced by subjecting the compound (43) to reaction with the compound (44) : [, wherein, in the formula, L 10 represents leaving groups such as a chlorine atom, a bromine atom, an iodine atom, p-toluenesulfonyloxy group, a methanesulfonyloxy group and the like; R 34 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group or a C3-C6 cycloalkyl group; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and W 1
- Said reaction is usually carried out in a solvent with the presence of a base.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar range applied to the compound (44) is usually from 1 to 3 moles per 1 mole of the compound (43) and that to the base is usually from 1 to 5 moles.
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from 0 to 150 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (45).
- post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (45).
- the isolated compound (45) can be purified by a technique such as chromatography, recrystallization and the like.
- Said reaction is usually carried out in a solvent, and if necessary, in the presence of a base.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters butylacetate, ethylacetate and the like; alcohols such as methanol, ethanol, propanol and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate and the like
- tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like
- nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar range applied to the base is usually from the catalytic amount to 10 moles per 1 mole of the compound (25) and that to the compound (18) or the salt thereof is usually from 1 to 10 moles.
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from 0 to 150 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, and if necessary, the organic layer being washed by acidic water and the like, subsequently drying and concentrating the organic layer, to isolate the compound (51).
- the isolated compound (51) can be purified by a technique such as chromatography, recrystallization and the like.
- Said reaction is carried out in a solvent with the presence of a catalyst.
- the solvent used for the reaction includes alcohols such as methanol, ethanol, propanol, butanol, 2-propanol and the like; ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; water and the mixture thereof.
- alcohols such as methanol, ethanol, propanol, butanol, 2-propanol and the like
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- aliphatic hydrocarbons such as hexane, heptane, octane and the like
- the catalyst used for the reaction includes palladium acetate, tetrakistriphenylphosphine palladium, ⁇ 1,1'-bis(diphenylphosphino)ferrocene ⁇ dichloropalladium methylene chloride complex and bis (triphenylphosphine) palladium dichloride.
- the molar range applied to the compound (27) is usually from 1 to 5 moles per 1 mole of the compound (51) and that to the catalyst is usually from 0.001 to 0.1 moles.
- Said reaction may be, if necessary, carried out in the presence of a base (, which includes inorganic base such as sodium acetate, potassium acetate, potassium carbonate, tripotassium phosphate, sodium bicarbonate and the like) and/or a phase-transfer catalyst (, which includes quaternary ammonium salts such as tetrabutylammonium bromide, benzyltriethylammonium bromide and the like).
- a base which includes inorganic base such as sodium acetate, potassium acetate, potassium carbonate, tripotassium phosphate, sodium bicarbonate and the like
- a phase-transfer catalyst which includes quaternary ammonium salts such as tetrabutylammonium bromide, benzyltriethylammonium bromide and the like.
- the reaction time is usually in the range of from 0.5 to 24 hours, and the reaction temperature is in the range of from 50 to 120 °C.
- the compound (52) can be isolated by being subjected to post treatment procedure exemplified below.
- the isolated compound (52) can be purified by technique such as chromatography, recrystallization and the like.
- the compound (3) can be produced, for example, according to the following (Intermediate Compound Production Method 1) or (Intermediate Compound Production Method 2).
- L 6 represents a chlorine atom, a bromine atom and an iodine atom
- the compound (30) can be produced by subjecting the compound (29) to reaction with the compound (27).
- Said reaction is carried out in a solvent with the presence of a catalyst.
- the solvent used for the reaction includes, alcohols such as methanol, ethanol, propanol, butanol, 2-propanoland and the like; ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; water and the mixture thereof.
- alcohols such as methanol, ethanol, propanol, butanol, 2-propanoland and the like
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- aliphatic hydrocarbons such as hexane, heptane, octane and the
- the catalyst used for the reaction includes palladium acetate, tetrakistriphenylphosphine palladium, ⁇ 1,1' -bis(diphenylphosphino)ferrocene ⁇ dichloropalladium methylene chloride complex and bis(triphenylphosphine) palladium dichloride.
- the molar ratio applied to the compound (27) is usually from 1 to 5 moles per 1 mole of the compound (29) and that to the catalyst is usually from 0.001 to 0.1 moles.
- Saidreaction maybe, if necessary, carried out in the presence of a base (, which includes inorganic base such as sodium acetate, potassium acetate, potassium carbonate, tripotassium phosphate, sodium bicarbonate and the like) and/or a phase-transfer catalyst (, which includes quaternary ammonium salts such as tetrabutylammonium bromide, benzyltriethylammonium bromide and the like).
- a base which includes inorganic base such as sodium acetate, potassium acetate, potassium carbonate, tripotassium phosphate, sodium bicarbonate and the like
- a phase-transfer catalyst which includes quaternary ammonium salts such as tetrabutylammonium bromide, benzyltriethylammonium bromide and the like.
- the reaction time is usually in the range of from 0.5 to 24 hours, and the reaction temperature is in the range of from 50 to 120 °C.
- the compound (30) can be isolated by being subjected to post treatment procedure exemplified below.
- the isolated compound (30) can be purified by a technique chromatography, recrystallization and the like.
- the compound (3) can be produced by subjecting the compound (30) to reduction reaction.
- Said reduction reaction includes a method to reduce the compound (30) by hydrogen in the presence of hydrogenation catalyst (, said method is referred to as (Step I-2-1) hereinafter), and a method to reduce the compound (30) by iron in the presence of an acidic water (, said method is referred to as (Step I-2-2) hereinafter).
- reaction of this step is usually carried out in a solvent.
- the solvent used for the reaction of the present step includes alcohols such as methanol, ethanol and the like; and ethers such as 1,4-dioxane, tetrahydrofuran and the like.
- the hydrogenation catalyst used for the reaction includes palladium catalysts such as palladium-carbon and platinum catalysts such as platinum-carbon.
- the molar ratio applied to hydrogen is usually from 3 to 10 moles per 1 mole of the compound (30) and that to the catalyst is usually from 0.001 to 0.1 moles.
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from 20 to 50 °C.
- the reaction mixture is subjected to post treatment procedure such as filtrating, subsequently concentrating the filtrate, to isolate the compound (3).
- the isolated compound (3) can be purified by a technique such as chromatography, recrystallization and the like.
- the acidic waters used for the reaction in this step include aqueous acetic acid, diluted hydrochloric acid, aqueous sulfuric acid and the like.
- the reaction may be, if necessary, carried out in the presence of esters such as ethylacetate and the like; and ethers such as tetrahydrofuran and the like.
- esters such as ethylacetate and the like
- ethers such as tetrahydrofuran and the like.
- the iron used for the reaction is usually used in the form of powder.
- the molar ratio applied to the iron is usually from 6 to 30 moles per 1 mole of the compound (30).
- the reaction time is usually in the range of from 0.1 to 10 hours, and the reaction temperature is in the range of from 40 to 100 °C.
- the reaction mixture is subjected to filtration, the filtrate obtained being washed by a basic water (such as aqueous saturated sodium bicarbonate and the like) and then being subjected to extraction with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (3).
- a basic water such as aqueous saturated sodium bicarbonate and the like
- organic solvent such as aqueous saturated sodium bicarbonate and the like
- the isolated compound (3) can be purified by a technique such as chromatography, recrystallization and the like.
- L 7 represents a chlorine atom, a bromine atom and an iodine atom
- L 8 represents a C1-C5 alkylcarbonyl group (an acetyl group, a pivaloyl group and the like)
- the compound (32) can be produced by subjecting the compound (31) to reaction with the compound (27).
- Said reaction is carried out in a solvent with the presence of a catalyst.
- the solvent used for the reaction includes alcohols such as methanol, ethanol, propanol, butanol, 2-propanol and the like; ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; and water and the mixture thereof.
- alcohols such as methanol, ethanol, propanol, butanol, 2-propanol and the like
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- aliphatic hydrocarbons such as hexane, heptane, octane and the like
- the catalyst used for the reaction includes palladium acetate, tetrakistriphenylphosphine palladium, ⁇ 1,1' -bis(diphenylphosphino)ferrocene ⁇ dichloropalladium methylene chloride complex and bis(triphenylphosphine) palladium dichloride.
- the molar ratio applied to the compound (27) is usually from 1 to 5 moles per 1 mole of the compound (31) and that to the catalyst is usually from 0.001 to 0.1 moles.
- Said reaction maybe, if necessary, carried out in the presence of a base (, which includes inorganic base such as sodium acetate, potassium acetate, potassium carbonate, tripotassium phosphate, sodium bicarbonate and the like) and/or a phase-transfer catalyst (, which includes quaternary ammonium salts such as tetrabutylammonium bromide, benzyltriethylammonium bromide and the like).
- a base which includes inorganic base such as sodium acetate, potassium acetate, potassium carbonate, tripotassium phosphate, sodium bicarbonate and the like
- a phase-transfer catalyst which includes quaternary ammonium salts such as tetrabutylammonium bromide, benzyltriethylammonium bromide and the like.
- the reaction time is usually in the range of from 0.5 to 24 hours, and the reaction temperature is in the range of from 50 to 120 °C.
- the compound (32) can be isolated by being subjected to post treatment procedure exemplified below.
- the compound (3) can be produced by subjecting the compound (32) tohydrolysis in the presence of abase (suchassodiumhydroxide, potassium hydroxide and the like).
- abase such as sodiumhydroxide, potassium hydroxide and the like.
- the reaction is carried out in a solvent.
- the solvent used for the reaction includes mixtures with water and alcohols such as methanol, ethanol and the like or ethers such as 1,4-dioxane and the like.
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from 20 to 100 °C.
- reaction mixture After completion of the reaction, the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (3).
- post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (3).
- the isolated compound (3) can be purified by a technique such as chromatography, recrystallization and the like.
- the compound (2) can be produced according to the (Intermediate Compound Production Method 3). That is, the compound (2) can be produced by subjecting the compound (34) to reaction with a halogenating agent (such as thionyl chloride, thionyl bromide and the like).
- a halogenating agent such as thionyl chloride, thionyl bromide and the like.
- L 1 represents a chlorine atom or a bromine atom
- R 1 , R 2 , R 3 , R 4 , R 5 and Q represent same meaning defined in [Invention 1].
- Said reaction is usually carried out in a solvent.
- the solvent used for the reaction includes aromatic hydrocarbons such as toluene, xylene and the like.
- the molar ratio applied to the halogenating agent is usually from 1 to 5 moles per 1 mole of the compound (34).
- the reaction time is usually in the range of from 0.5 to 24 hours, and the reaction temperature is in the range of from 50 to 120 °C.
- the compound (2) can be isolated from the reaction mixture by being subjected to post treatment procedure such as concentration and the like.
- Some of the compound (34) can be produced according to the methods described in International Publication WO01/95721, International Publication WO00/41998, International Publication WO96/23763 or International Publication WO96/31464.
- the compound (50) among the compound (34) can be produced according to (Intermediate Compound Production Method 4).
- R 1 , R 2 , R 3 , R 4 and R 5 represent same meaning defined in [Invention 1] and R 15 represents same meaning described above.
- the compound (36) can be produced by subjecting the compound (35) to react with a reducing agent.
- the reducing agent used for the reaction includes sodium borohydride and potassium borohydride.
- the solvent used for the reaction includes alcohols such as methanol, ethanol, 2-propanol and the like; ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like ; aromatic hydrocarbons such as toluene, xylene and the like ; and water and the mixture thereof.
- alcohols such as methanol, ethanol, 2-propanol and the like
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- aliphatic hydrocarbons such as hexane, heptane, octane and the like
- aromatic hydrocarbons such as toluene, xylene and
- the molar ratio applied to the reducing agent is usually from 0.25 to 3 moles per 1 mole of the compound (35).
- the reaction time is usually in the range of from the instant to 24 hours, and the reaction temperature is in the range of from -20 to 100 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (36).
- the isolated compound (36) can be purified by a technique such as chromatography, recrystallization and the like.
- the compound (37) can be produced by subjecting the compound (36) to react with methanesulfonylchloride.
- Said reaction is carried out with the presence of a base usually in a solvent.
- the solvent used for the reaction includes, ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar ratio applied to methanesulfonyl chloride is usually from 1 to 3 moles per 1 mole of the compound (36) and that of the base is usually from 1 to 10 moles.
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from -20 to 100 °C.
- reaction mixture is subjected to post treatment procedure such as concentration, the concentrated residue being added with an organic solvent to be filtrated, subsequently concentrating the filtrate, to isolate the compound (37).
- the compound (39) can be produced by subjecting the compound (37) to react with the compound (38).
- Said reaction is usually carried out in a solvent with the presence of a base.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar ratio applied to the compound (38) is usually from 1 to excessive amount per 1 mole of the compound (37) and that of the base is usually from the catalytic amount to 5 moles.
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from 50 to 150 °C.
- the compound (39) can be isolated by being subjected to post treatment procedure exemplified below.
- the compound (50) can be produced by subjecting the compound (39) to hydrolysis in the presence of a base (such as sodium hydroxide, potassium hydroxide and the like).
- a base such as sodium hydroxide, potassium hydroxide and the like.
- the reaction is usually carried out in a solvent such as mixture of water and an alcohol (, for example, methanol, ethanol and the like) and the like.
- a solvent such as mixture of water and an alcohol (, for example, methanol, ethanol and the like) and the like.
- the molar ratio applied to the base is usually from 1 to 20 moles per 1 mole of the compound (39).
- the reaction time is usually in the range of from 0.5 to 24 hours, and the reaction temperature is in the range of from 0 to 120 °C.
- the reaction mixture is subjected to post treatment procedure, such as, after being made acidity with an acid such as hydrochloric acid and the like, extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (50).
- post treatment procedure such as, after being made acidity with an acid such as hydrochloric acid and the like, extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (50).
- the isolated compound (50) can be purified by a technique such as chromatography, recrystallization and the like.
- R 1 , R 4 and R 5 are hydrogen atoms and R 15 is a 2-propynyl group
- R 2 and R 3 independently represent a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 haloalkenyl group, a C2-C6 alkynyl group, a C2-C6 haloalkynyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C3-C6 alkenyloxy group, a C3-C6 haloalkenyloxy group, a C3-C6 alkynyloxy group, a C3-C6 haloalkynyl
- the compound (43) can be produced according to, for example, (Intermediate Compound Production Method 5).
- L 11 represents a chlorine atom or a bromine atom
- L 12 and L 13 are same or different each other and represent an alkoxy group such as a methoxy group and the like;
- the compound (48) can be produced by subjecting the compound (46) to react with the compound (47).
- Said reaction is usually carried out in a solvent with the presence of a base.
- the solvent used for the reaction includes, ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar ratio applied to the compound (47) is usually from 0.5 to 2 moles per 1 mole of the compound (46) and that to the base is from 1 to 10 moles.
- the reaction time is usually in the range of from 0.1 to 24 hours, and the reaction temperature is in the range of from 0 to 150 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (48).
- the isolated compound (48) can be purified by a technique such as chromatography, recrystallization and the like.
- the compound (49) can be produced by subjecting the compound (48) to react with the compound (48-1) or the compound (48-2).
- Said reaction is usually carried out in a solvent.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, t-butylmethylether and the like, aliphatic hydrocarbons such as hexane, heptane and the like, aromatic hydrocarbons such as toluene and the like, halogenated hydrocarbons such as chlorobenzene and the like, organic bases such as pyridine, triethylamine, N,N-dimethylaniline and the like, N,N-dimethylformamide or the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, t-butylmethylether and the like
- aliphatic hydrocarbons such as hexane, heptane and the like
- aromatic hydrocarbons such as toluene and the like
- halogenated hydrocarbons such as chlorobenz
- the molar ratio applied to the compound (48-1) or the compound (48-2) is usually from 1 to 10 moles per 1 mole of the compound (48).
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from 50 to 150 °C.
- reaction mixture After completion of the reaction, the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (49).
- post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (49).
- the isolated compound (49) can be purified by a technique such as chromatography, recrystallization and the like.
- the compound (43) can be produced by subjecting the compound (49) to react with water in the presence of an acid.
- Said reaction may be carried out in water as the solvent or in the mixture of water and other organic solvents.
- the other organic solvents include ethers such as 1, 4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, t-butylmethylether and the like, aliphatic hydrocarbons such as hexane, heptane and the like, aromatic hydrocarbons such as toluene and the like, halogenated hydrocarbons such as chlorobenzene and the like, organic nitriles such as acetonitrile and the like; N,N-dimethylformamide, dimethylsulfoxide and the mixture thereof.
- ethers such as 1, 4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, t-butylmethylether and the like
- aliphatic hydrocarbons such as hexane, heptane and the like
- aromatic hydrocarbons such as toluene and the like
- halogenated hydrocarbons such as chlorobenzene and the like
- the acid used for the reaction includes hydrochloric acid, sulfuric acid, p-toluenesulfonic acid and the like.
- the molar ratio applied to the acid is usually from 0.1 to 100 moles per 1 mole of the compound (49).
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from 20 to 100 °C.
- reaction mixture After completion of the reaction, the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (43).
- post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the compound (43).
- the isolated compound (43) can be purified by a technique such as chromatography, recrystallization and the like.
- the compound (26) can be produced according to (Intermediate Compound Production Method 6).
- L 4 represents a chlorine atom or a bromine atom
- L 5 represents a chlorine atom, a bromine atom or an iodine atom
- the compound (25) can be produced by subjecting the compound (23) to react with the compound (24).
- Said reaction is usually carried out in a solvent with the presence of a base.
- the solvent used for the reaction includes ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as ethylacetate, butylacetate and the like; organic nitriles such as acetonitrile, butyronitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the
- the base used for the reaction includes carbonates such as sodium carbonate, potassium carbonate and the like; tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; and nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- carbonates such as sodium carbonate, potassium carbonate and the like
- tertiary amines such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like
- nitrogen-contained aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
- the molar ratio applied to the compound (23) is usually from 1 to 3 moles per 1 mole of the compound (23) and that of the base is usually from 1 to 10 moles.
- the reaction time is usually in the range of from 1 to 24 hours, and the reaction temperature is in the range of from -20 to 100 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent, if necessary, the organic layer being washed by acidic water, basic water and the like, subsequently drying and concentrating the organic layer, to isolate the compound (25).
- post treatment procedure such as extracting with organic solvent, if necessary, the organic layer being washed by acidic water, basic water and the like, subsequently drying and concentrating the organic layer, to isolate the compound (25).
- the isolated compound (25) can be purified by a technique such as chromatography, recrystallization and the like.
- the compound (26) can be produced by subjecting the compound (25) to react with a reducing agent.
- the reducing agent used for the reaction includes sodium borohydride and potassium borohydride.
- the solvent used for the reaction includes alcohols such as methanol, ethanol, 2-propanol and the like; ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; water and the mixture thereof.
- alcohols such as methanol, ethanol, 2-propanol and the like
- ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether, tert-butylmethylether and the like
- aliphatic hydrocarbons such as hexane, heptane, octane and the like
- aromatic hydrocarbons such as toluene, xylene and the like
- the molar ratio applied to the reducing agent is usually from 0.25 to 3 moles per 1 mole of the compound (25).
- the reaction time is usually in the range of from the instant to 24 hours, and the reaction temperature is in the range of from -20 to 100 °C.
- the reaction mixture is subjected to post treatment procedure such as extracting with organic solvent after being added to an acidic water such as aqueous saturated ammonium chloride and the like, the organic layer obtained being washed by basic water, subsequently drying and concentrating the organic layer, to isolate the compound (26).
- the isolated compound (26) can be purified by a technique such as chromatography, recrystallization and the like.
- Plant diseases against which the compound of the present invention has controlling activity include, for example, a disease due to Phycomycetes, specifically following diseases are illustrated:
- the fungicidal composition of the present invention comprises the compound of the present invention and a carrier.
- the carrier is inert to the compound of the present invention and appropriately chosen depending on types applying the fungicidal composition of the present invention and the like.
- the fungicidal composition of the present invention may further comprise adjuvant for formulation such as surfactant and the like depending on the necessity.
- the fungicidal composition of the present invention includes formulation forms such as emulsifiable concentrate, wettable powder, dry flowable, flowable, dust, granule and the like.
- the fungicidal composition of the present invention usually contains 0.1 to 90 % by weight of the compound of the present invention.
- Solid carriers used for the fungicidal composition of the present invention include, for example, fine powders or granules of minerals such as kaolin clay, attapulgite clay, bentonite, montmorillonite, terra alba, pyrophyllite, talc, diatomaceous earth, calcite and the like; natural organic substances such as corncob powder, walnut shell powder and the like; synthetic organic substances such as urea and the like; salts such as calcium carbonate, ammonium sulfate and the like; synthetic inorganic substances such as synthetic hydrous silicon oxide and the like.
- minerals such as kaolin clay, attapulgite clay, bentonite, montmorillonite, terra alba, pyrophyllite, talc, diatomaceous earth, calcite and the like
- natural organic substances such as corncob powder, walnut shell powder and the like
- synthetic organic substances such as urea and the like
- salts such as calcium carbonate, ammonium sulf
- Liquid carriers include, for example, aromatic hydrocarbons such as xylene, alkylbenzene, methylnaphthalene and the like; alcohols such as 2-propanol, ethylene glycol, propylene glycol, cellosolve and the like; ketones such as acetone, cyclohexanone, isophorone and the like; vegetable oils such as soybean oil, cottonseed oil and the like; petroleum aliphatic hydrocarbons, esters, dimethylsulfoxide, acetonitrile and water.
- aromatic hydrocarbons such as xylene, alkylbenzene, methylnaphthalene and the like
- alcohols such as 2-propanol, ethylene glycol, propylene glycol, cellosolve and the like
- ketones such as acetone, cyclohexanone, isophorone and the like
- vegetable oils such as soybean oil, cottonseed oil and the like
- Surfactants include, for example, anionic surfactants such as alkylsulfuric acid ester salt, alkylarylsulfonic acid salt, dialkylsulfosuccinic acid salt, polyoxyethylenealkylaryletherphosphoric acid ester salt, lignin sulfonic acid salt, polycondensed naphthalenesulfonateformaldehyde and the like; and nonionic surfactants such as polyoxyethylenealkylarylether, polyoxyethylenealkylpolyoxypropylene block copolymer, sorbitan fatty acid ester and the like.
- anionic surfactants such as alkylsulfuric acid ester salt, alkylarylsulfonic acid salt, dialkylsulfosuccinic acid salt, polyoxyethylenealkylaryletherphosphoric acid ester salt, lignin sulfonic acid salt, polycondensed naphthalenesulfonateformaldehyde and the like
- Another adjuvant for formulation includes, for example, water-soluble polymers such as polyvinylalcohol, polyvinylpyrrolidone and the like; Arabian gum; alginic acid and its salt thereof; polysaccharides such as CMC(carboxymethylcellulose), xanthan gum and the like; inorganic substances such as alminum magnesium silicate, alumina sol and the like; and antiseptics, colorants, PAP(isopropyl acidic phosphate), stabilizers such as BHT and the like.
- water-soluble polymers such as polyvinylalcohol, polyvinylpyrrolidone and the like
- Arabian gum alginic acid and its salt thereof
- polysaccharides such as CMC(carboxymethylcellulose), xanthan gum and the like
- inorganic substances such as alminum magnesium silicate, alumina sol and the like
- antiseptics, colorants, PAP(isopropyl acidic phosphate), stabilizers such as B
- fungicidal composition of the present invention By applying the fungicidal composition of the present invention to treatment for plants, said plants can be protected from plant diseases; and by applying the fungicidal composition of the present invention to treatment for soils, said plants grown on said soils can be protected from plant diseases.
- the application amount thereof which may be varied with a kind of control-object plants, a kind and an infestation level of control-object diseases, formulation types, application timings, weather conditions and the like, is usually 1 to 5000 g of the compound of the present invention per 10000 m 2 , preferably 5 to 1000 g.
- Emulsifiable concentrate, wettable powder, flowable and the like are usually sprayed after diluted with water.
- concentration of the compound of the present invention is usually in the range of from 0.0001 to 3 % by weight, preferably from 0.0005 to 1 % by weight. Dust, granule and the like are usually directly used without dilution.
- the fungicidal composition of the present invention can be also applied in treatment methods such as seed disinfection and the like.
- the methods include, for example, a method to soak seeds of a plant in the liquid fungicidal composition of the present invention which prepared in 1 to 1000 ppm in terms of concentration of the compound of the present invention, a method to spray or coat seeds of a plant with the liquid fungicidal composition of the present invention which prepared in 1 to 1000 ppm in terms of concentration of the compound of the present invention, and a method to coat seeds of a plant with the powder of the composition controlling plant diseases of the present invention.
- the method for controlling plant diseases of the present invention is performed by applying effective amount of the compound of the present invention to a plant or a soil growing the plant in which infection is predictable and/or to a plant or a soil growing the plant in which infection is confirmed.
- the fungicidal composition of the present invention is usually used as an agent controlling plant diseases for agriculture or gardening, that is, as an agent controlling plant diseases to control plant diseases on plowed fields, paddy fields, orchards, tea fields, pastures, lawn and the like.
- the fungicidal composition of the present invention may be used together with other plant disease controlling compositions, pesticides, acaricides, nematicides, herbicides, plant growth regulators and/or fertilizers.
- Examples of the active ingredient of such other plant diseases controlling composition include:
- reaction mixture was cooled down to room temperature, and then the reaction mixture was added with water to be extracted by ethylacetate.
- the organic layer was successively washed by aqueous saturated sodium bicarbonate and aqueous saturated sodium chloride and then dried by magnesium sulfate, followed by concentration under reduced pressure to obtain 1.0 g of N-(2-chloropyridine-3-yl)-2-hydroxy-2-(4-chlorophenyl)acetami de.
- the organic layer was washed by 1 % hydrochloric acid and water, and then dried by magnesium sulfate, followed by concentration under reduced pressure to obtain N- ⁇ 2-(3,4-dimethoxyphenyl)pyridine-3-yl ⁇ -2-methanesulfonyloxy -2-(4-chlorophenyl)acetamide (, which is referred to as the compound of the present invention (1-3) hereinafter).
- N-(2-chloropyridine-3-yl)-2-oxo-2-(4-methylphenyl)acetamide was dissolved and then added with 62 mg of sodium borohydride at 0 °C, followed by stirring at room temperature for 3 hours. Thereafter, the reaction mixture was added with aqueous saturated ammonium chloride to be extracted by ethylacetate. The organic layer was successively washed by aqueous saturated sodium bicarbonate and aqueous saturated sodium chloride, and then dried by magnesium sulfate, followed by concentration under reduced pressure to obtain 285 mg of N-(2-chloropyridine-3-yl)-2-hydroxy-2-(4-methylphenyl)acetami de.
- N- ⁇ 2-(3,4-dimethoxyphenyl)pyridine-3-yl ⁇ -2-methanesulfonyloxy -2-(4-methylphenyl)acetamide (, which is referred to as the compound of the present invention (1-5) hereinafter).
- This N- ⁇ 2-(3,4-dimethoxyphenyl)pyridine-3-yl ⁇ -2-methanesulfonyloxy -2-(4-methylphenyl)acetamide and 2.5 ml of 2-propyn-1-ol were mixed, followed by stirring at around 80 °C for 1 hour.
- reaction mixture was filtrated thruogh celite, followed by concentration of the filtrate under reduced pressure.
- the reaction solution was concentrated under reduced pressure to obtain a crude 2-(chlorophenyl)-3,3-dichloroacryl chloride.
- the crude 2-(chlorophenyl)-3,3-dichloroacryl chloride obtained was added dropwise to 10 ml of tetrahydrofuran solution containing of 0.50 g of triethylamine and 0.30 g of 3-amino-2-(3,4-dimethoxyphenyl)pyridine, followed by stirring at room temperature for 3 hours; and then the reaction solution was added with ethylacetate and then filtrated to remove insolubles.
- Parts represent parts by weight.
- control effect was evaluated by visually observing the area of a lesion on a sample plant in investigation and comparing the area of a lesion on a non-treatment plant and the area of a lesion on a treated plant with the compound of the present invention.
- the liquid on the stem was air-dried, and a suspension of zoosporangiua of Phytophthora infestans (about 10,000 zoosporangiua were contained in 1ml of the suspension) was inoculated by spraying.
- the amount of the sprayed suspension was about 2 ml for one plent.
- the plant was first grown for one day at 23°C under 90 % or more humidity, then further grown for 4 days in the green house, which was 24°C in daytime and 20°C in night-time.
- the lesion areas on the plants treated with the compounds of the present invention were not more than 10% of the lesion area on a non-treatment plant.
- Sand loam was compacted in a plasticpot, andatomato (variety: Ponterosa) was seeded and grown in a green house for 20 days.
- the compounds of the present invention (I-11) was formulatedto flowable according to Formulation Example 6, then, diluted with water to provide given concentration of 200ppm, and this diluted solution was sprayed onto stems and leaves so as to give sufficient adhesion on the surface of the tomato leaves. After spraying, the liquid on the stem was air-dried, and a suspension of zoosporangiua of Phytophthora infestans (about 10,000 zoosporangiua were contained in 1ml of the suspension) was inoculated by spraying.
- the amount of the sprayed suspension was about 2 ml for one plent. After inoculation, the plant was first grown for one day at 23°C under 90 % or more humidity, then further grown for 4 days in the green house, which was 24°C in daytime and 20°C in night-time.
- the lesion areas on the plants treated with the compounds of the present invention (I-11) was not more than 10% of the lesion area on a non-treatment plant.
- the liquid on the stem was air-dried, and a suspension of zoosporangiua of Plasmopara viticola (about 10,000 zoosporangiua were contained in 1ml of the suspension) was inoculated by spraying.
- the amount of the sprayed suspension was about 2 ml for one plant.
- the plant was first grown for one day at 23°C under 90 % or more humidity, then further grown for 6 days in the green house, which was 24°C in daytime and 20°C in night-time.
- the lesion areas on the plants treated with the present compound (I-1), (I-2), (I-6) to (I-12), (II-1), (III-1) and (IV-1) were not more than 10% of the lesion area on a non-treatment plant.
- Sand loam was compacted in a plasticpot, and a grape (variety: Berry A) was seeded and grown in a green house for 40 days.
- the compounds of the present invention (I-4) was formulated to flowable according to Formulation Example 6, then, diluted with water to provide given concentration of 200ppm, and this diluted solution was sprayed onto stems and leaves so as to give sufficient adhesion on the surface of grape leaves. After spraying, the liquid on the stem was air-dried, and a suspension of zoosporangiua of Plasmopara viticola (about 10,000 zoosporangiua were contained in 1ml of the suspension) was inoculated by spraying. The amount of the sprayed suspension was about 2 ml for one plant. After inoculation, the plant was first grown for one day at 23°C under 90 % or more humidity, then further grown for 6 days in the green house, which was 24°C in daytime and 20°C in night-time.
- the lesion areas on the plants treated with the present compound (I-4) was not more than 10% of the lesion area on a non-treatment plant.
- the compound of the present invention has an excellent controlling activity against plant diseases and is useful as an active ingredient for the agent controlling plant diseases.
Abstract
A phenylpyridine compound represented by the formula has
an excellent controlling activity against plant diseases:
[, wherein, in the formula, R1, R2, R3, R4 and R5 independently
represent a hydrogen atom, a halogen atom and the like; R6 represents
a hydrogen atom or a C1-C3 alkyl group; R7, R8 and R11 independently
represent a hydrogen atom, a halogen atom and the like; R9 and R10
independently represent a hydroxyl group and the like; W1―W2=W3
―W4 represents N―CH=CH―CH and the like; X represents an oxygen
atom and the like; and Q represents a (C1-C6 alkoxy)methylene and
the like].
Description
The present invention relates a phenylpyridine compound and
a fungicidal composition comprising the same.
Various compounds having controlling activity against plant
diseases are conventionally developed and provided in practical
use as an active ingredient of the fungicidal composition, however
sometimes their controlling activity are not always enough.
The inventor (s) of the present invention, after intensively
studying, has found that a phenylpyridine compound (1) represented
by the following formula has an excellent controlling activity
against plant diseases and accomplished the present invention.
The present invention provides:
R6 represents a hydrogen atom or a C1-C3 alkyl group; R7, R8 and R11 independently represent a hydrogen atom, a halogen atom or a C1-C3 alkyl group;
R9 and R10 independently represent a hydroxyl group, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 haloalkenyl group, a C2-C6 alkynyl group, a C2-C6 haloalkynyl group, a C2-C6 cyanoalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C3-C6 alkenyloxy group, a C3-C6 haloalkenyloxy group, a C3-C6 alkynyloxy group, a C3-C6 haloalkynyloxy group, a C2-C6 cyanoalkyloxy group, a C1-C6 alkylthio group, a C1-C6 haloalkylthio group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group, a nitro group, a benzyl group or a cyano group; W1―W2=W3 ―W4 represents N―CR21=CR22―CR23, CR24―N=CR25―CR26, CR27―CR28=N― CR29 or CR30―CR31=CR32―N
{in which R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31 and R32 independently represent a hydrogen atom, a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group, a C1-C3 haloalkyl group}:
X represents an oxygen atom or a sulfur atom;
Q represents a group illustrated by the following formulas of Q1 or Q2 {in which R14 represents a hydrogen atom or a C1-C3 alkyl group, R15 represents a hydrogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group, a C3-C6 cycloalkyl group, a (C1-C6 alkyl)carbonyl group, a (C1-C6 haloalkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a (C1-C6 haloalkoxy) carbonyl group, a (C3-C6 alkenyloxy) carbonyl group, a (C3-C6 haloalkenyloxy)carbonyl group, a (C3-C6 alkynyloxy)carbonyl group, a (C3-C6 haloalkynyloxy) carbonyl group or a C1-C3 alkylsulfonyl group,
Z1 represents an oxygen atom or a sulfur atom,
Z2 represents an oxygen atom, NOR16 (in which R16 represents a hydrogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group or a C3-C6 cycloalkyl group), CR17R18 (in which R17 represents a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C3-C6 alkenyloxy group, a C3-C6 haloalkenyloxy group, a C3-C6 alkynyloxy group, a C3-C6 haloalkynyloxy group or a C3-C6 cycloalkyloxy group and R18 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group) or NNR19R20 (in which R19 and R20 independently represent a hydrogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group or a C3-C6 cycloalkyl group)}];
(referred to as "the compound of the present invention" hereinafter.);
In the representation of R1, R2, R3, R4 and R5, the halogen
atom includes a fluorine atom, a chlorine atom, a bromine atom
and the like;
the C1-C6 alkyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a hexyl group and the like;
the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorodifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a trichloromethyl group, a dichlorobromomethyl group, a pentafluoroethyl group, a 2,2,2-trifluoroethyl group, a 1,1-difluoroethyl group, a 2,2-difluoroethyl group, a 2-fluoroethyl group, a 6,6,6-trifluorohexyl group and the like;
the C2-C6 alkenyl group includes a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-methyl-1-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-1-propenyl group, a 2-methyl-2-propenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 1-hexenyl group, a 2-hexenyl group, a 5-hexenyl group and the like;
the C2-C6 haloalkenyl group includes a 1-chlorovinyl group, a 2-chlorovinyl group, a 2,2-dichlorovinyl group, a 2,2-difluorovinyl group, a 1,2-dichlorovinyl group, a 3,3-dichloro-2-propenyl group, a 3,3-difluoro-2-propenyl group and the like;
the C2-C6 alkynyl group includes an ethynyl group, a 2-propynyl group, a 3-butynyl group, a 3-hexynyl group, a 5-hexynyl group and the like;
the C2-C6 haloalkynyl group includes a 2-chloroethynyl group, a 2-bromoethynyl group, a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 6-chloro-5-hexynyl group and the like; the C1-C6 alkoxy group includes a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, an isopentyloxy group, a hexyloxy group and the like;
the C1-C6 haloalkoxy group includes a trifluoromethoxy group, a difluoromethoxy group, a bromodifluoromethoxy group, a chlorodifluoromethoxy group, a fluoromethoxy group, a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, a 5-chloropentyloxy group, a 4-fluoroisopentyloxy group, a 2,2-dichlorohexyloxy group and the like;
the C3-C6 alkenyloxy group includes a 2-propenyloxy group, a 1-methyl-2-propenyloxy group, a 2-methyl-2-propenyloxy group, a 2-butenyloxy group, a 3-butenyloxy group, a 2-hexenyloxy group, a 5-hexenyloxy group and the like;
the C3-C6 haloalkenyloxy group includes a 3,3-dichloro-2-propenyloxy group, a 3,3-difluoro-2-propenyloxy group, a 3,3-dibromo-2-propenyloxy group, a 2,3-dichloropropenyloxy group, a 6-fluoro-2-hexenyloxy group, a 2,2-dichloro-5-hexenyloxy group and the like;
the C3-C6 alkynyloxy group includes a 2-propynyloxy group, a 1-methyl-2-propynyloxy group, a 2-butynyloxy group, a 3-butynyloxy group, a 2-hexynyloxy group, a 5-hexynyloxy group and the like;
the C3-C6 haloalkynyloxy group includes a 3-chloro-2-propynyloxy group, a 3-bromo-2-propynyloxy group, a 3-iodo-2-propynyloxy group, a 6-chloro-5-hexynyloxy group and the like;
the C1-C6 alkylthio group includes a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, an isobutylthio group, a sec-butylthio group, a
tert-butylthio group, a pentylthio group, an isopentylthio group, a hexylthio group and the like;
the C1-C6 haloalkylthio group includes a trifluoromethylthio group, a difluoromethylthio group, a bromodifluoromethylthio group, a chlorodifluoromethylthio group, a fluoromethylthio group, a 2,2,2-trifluoroethylthio group, a 1,1,2,2-tetrafluoroethylthio group, a 5-chloropentylthio group, a 4-fluoroisopentylthio group, a 2,2-dichlorohexylthio group and the like;
the C3-C6 cycloalkyl group includes a cyclopropyl group, a cyclopentyl group, a cyclohexyl group and the like; and
the C3-C6 cycloalkoxy group includes a cyclopropoxy group, a cyclopentyloxy group, a cyclohexyloxy group and the like.
the C1-C6 alkyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a hexyl group and the like;
the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorodifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a trichloromethyl group, a dichlorobromomethyl group, a pentafluoroethyl group, a 2,2,2-trifluoroethyl group, a 1,1-difluoroethyl group, a 2,2-difluoroethyl group, a 2-fluoroethyl group, a 6,6,6-trifluorohexyl group and the like;
the C2-C6 alkenyl group includes a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-methyl-1-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-1-propenyl group, a 2-methyl-2-propenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 1-hexenyl group, a 2-hexenyl group, a 5-hexenyl group and the like;
the C2-C6 haloalkenyl group includes a 1-chlorovinyl group, a 2-chlorovinyl group, a 2,2-dichlorovinyl group, a 2,2-difluorovinyl group, a 1,2-dichlorovinyl group, a 3,3-dichloro-2-propenyl group, a 3,3-difluoro-2-propenyl group and the like;
the C2-C6 alkynyl group includes an ethynyl group, a 2-propynyl group, a 3-butynyl group, a 3-hexynyl group, a 5-hexynyl group and the like;
the C2-C6 haloalkynyl group includes a 2-chloroethynyl group, a 2-bromoethynyl group, a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 6-chloro-5-hexynyl group and the like; the C1-C6 alkoxy group includes a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, an isopentyloxy group, a hexyloxy group and the like;
the C1-C6 haloalkoxy group includes a trifluoromethoxy group, a difluoromethoxy group, a bromodifluoromethoxy group, a chlorodifluoromethoxy group, a fluoromethoxy group, a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, a 5-chloropentyloxy group, a 4-fluoroisopentyloxy group, a 2,2-dichlorohexyloxy group and the like;
the C3-C6 alkenyloxy group includes a 2-propenyloxy group, a 1-methyl-2-propenyloxy group, a 2-methyl-2-propenyloxy group, a 2-butenyloxy group, a 3-butenyloxy group, a 2-hexenyloxy group, a 5-hexenyloxy group and the like;
the C3-C6 haloalkenyloxy group includes a 3,3-dichloro-2-propenyloxy group, a 3,3-difluoro-2-propenyloxy group, a 3,3-dibromo-2-propenyloxy group, a 2,3-dichloropropenyloxy group, a 6-fluoro-2-hexenyloxy group, a 2,2-dichloro-5-hexenyloxy group and the like;
the C3-C6 alkynyloxy group includes a 2-propynyloxy group, a 1-methyl-2-propynyloxy group, a 2-butynyloxy group, a 3-butynyloxy group, a 2-hexynyloxy group, a 5-hexynyloxy group and the like;
the C3-C6 haloalkynyloxy group includes a 3-chloro-2-propynyloxy group, a 3-bromo-2-propynyloxy group, a 3-iodo-2-propynyloxy group, a 6-chloro-5-hexynyloxy group and the like;
the C1-C6 alkylthio group includes a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, an isobutylthio group, a sec-butylthio group, a
tert-butylthio group, a pentylthio group, an isopentylthio group, a hexylthio group and the like;
the C1-C6 haloalkylthio group includes a trifluoromethylthio group, a difluoromethylthio group, a bromodifluoromethylthio group, a chlorodifluoromethylthio group, a fluoromethylthio group, a 2,2,2-trifluoroethylthio group, a 1,1,2,2-tetrafluoroethylthio group, a 5-chloropentylthio group, a 4-fluoroisopentylthio group, a 2,2-dichlorohexylthio group and the like;
the C3-C6 cycloalkyl group includes a cyclopropyl group, a cyclopentyl group, a cyclohexyl group and the like; and
the C3-C6 cycloalkoxy group includes a cyclopropoxy group, a cyclopentyloxy group, a cyclohexyloxy group and the like.
In the representation of R6, the C1-C3 alkyl group includes
a methyl group, an ethyl group, a propyl group and the like.
In the representation of R7, R8 and R11, the halogen atom
includes a fluorine atom, a chlorine atom, a bromine atom and the
like.
the C1-C3 alkyl group includes a methyl group, an ethyl group, a propyl group and the like.
the C1-C3 alkyl group includes a methyl group, an ethyl group, a propyl group and the like.
In the representation of R9 and R10, the halogen atom includes
a fluorine atom, a chlorine atom, a bromine atom and the like;
the C1-C6 alkyl group includes a methyl group, an ethyl group,
a propyl group, an isopropyl group, a butyl group, an isobutyl
group, a sec-butyl group, a tert-butyl group, a pentyl group, an
isopentyl group, a hexyl group and the like;
the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorodifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a trichloromethyl group, a dichlorobromomethyl group, a pentafluoroethyl group, a 2,2,2-trifluoroethyl group, a 2,2-difluoroethyl group, a 2-fluoroethyl group, a 6,6,6-trifluorohexyl group and the like; the C2-C6 alkenyl group includes a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-methyl-1-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-1-propenyl group, a 2-methyl-2-propenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 1-hexenyl group, a 2-hexenyl group, a 5-hexenyl group and the like;
the C2-C6 haloalkenyl group includes a 1-chlorovinyl group, a 2-chlorovinyl group, a 2,2-dichlorovinyl group, a 2,2-difluorovinyl group, a 1,2-dichlorovinyl group, a 3, 3-dichloropropenyl group, a 3,3-difluoropropenyl group and the like;
the C2-C6 alkynyl group includes an ethynyl group, a 2-propynyl group, a 3-butynyl group, a 5-hexynyl group and the like;
the C2-C6 haloalkynyl group includes a 2-chloroethynyl group, a 2-bromoethynyl group, and a 6-chloro-5-hexynyl group and the like;
the C2-C6 cyanoalkyl group includes a cyanomethyl group, a 1-cyanoethyl group, a 2-cyanoethyl group and the like;
the C1-C6 alkoxy group includes a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, an isopentyloxy group, a hexyloxy group and the like;
the C1-C6 haloalkoxy group includes a trifluoromethoxy group, a difluoromethoxy group, a bromodifluoromethoxy group, a chlorodifluoromethoxy group, a fluoromethoxy group, a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, a 5-chloropentyloxy group, a 4-fluoroisopentyloxy group, a 2,2-dichlorohexyloxy group and the like;
the C3-C6 alkenyloxy group includes a 2-propenyloxy group, a 1-methyl-2-propenyloxy group, a 2-methyl-2-propenyloxy group, a 2-butenyloxy group, a 3-butenyloxy group, a 2-hexenyloxy group, a 5-hexenyloxy group and the like;
the C3-C6 haloalkenyloxy group includes a 3-chloro-2-propynyloxy group, a 3-bromo-2-propynyloxy group, a 3-iodo-2-propynyloxy group, a 6-chloro-5-hexenyloxy group and the like;
the C3-C6 alkynyloxy group includes a 2-propynyloxy group, a 1-methyl-2-propynyloxy group, a 2-butynyloxy group, a 3-butynyloxy group, a 2-hexynyloxy group, a 5-hexynyloxy group and the like;
the C3-C6 haloalkynyloxy group includes a 3-chloro-2-propynyloxy group, a 3-bromo-2-propynyloxy group, a 3-iodo-2-propynyloxy group, a 6-chloro-5-hexynyloxy group and the like;
the C2-C6 cyanoalkyloxy group includes a cyanomethyloxy group, a 1-cyanoethyloxy group, a 2-cyanoethyloxy group and the like;
the C1-C6 alkylthio group includes a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, an isobutylthio group, a sec-butylthio group, a
tert-butylthio group, a pentylthio group, an isopentylthio group, a hexylthio group and the like;
the C1-C6 haloalkylthio group includes a trifluoromethylthio group, a difluoromethylthio group, a bromodifluoromethylthio group, a chlorodifluoromethylthio group, a fluoromethylthio group, a 2,2,2-trifluoroethylthio group, a 1,1,2,2-tetrafluoroethylthio group, a 5-chloropentylthio group, a 4-f luoroisopentylthio group, a 2,2-dichlorohexylthio group and the like;
the C3-C6 cycloalkyl group includes a cyclopropyl group, a cyclopentyl group, a cyclohexyl group and the like; and
the C3-C6 cycloalkyloxy group includes a cyclopropyloxy group, a cyclopentyloxy group, a cyclohexyloxy group and the like.
the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorodifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a trichloromethyl group, a dichlorobromomethyl group, a pentafluoroethyl group, a 2,2,2-trifluoroethyl group, a 2,2-difluoroethyl group, a 2-fluoroethyl group, a 6,6,6-trifluorohexyl group and the like; the C2-C6 alkenyl group includes a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-methyl-1-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-1-propenyl group, a 2-methyl-2-propenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 1-hexenyl group, a 2-hexenyl group, a 5-hexenyl group and the like;
the C2-C6 haloalkenyl group includes a 1-chlorovinyl group, a 2-chlorovinyl group, a 2,2-dichlorovinyl group, a 2,2-difluorovinyl group, a 1,2-dichlorovinyl group, a 3, 3-dichloropropenyl group, a 3,3-difluoropropenyl group and the like;
the C2-C6 alkynyl group includes an ethynyl group, a 2-propynyl group, a 3-butynyl group, a 5-hexynyl group and the like;
the C2-C6 haloalkynyl group includes a 2-chloroethynyl group, a 2-bromoethynyl group, and a 6-chloro-5-hexynyl group and the like;
the C2-C6 cyanoalkyl group includes a cyanomethyl group, a 1-cyanoethyl group, a 2-cyanoethyl group and the like;
the C1-C6 alkoxy group includes a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, an isopentyloxy group, a hexyloxy group and the like;
the C1-C6 haloalkoxy group includes a trifluoromethoxy group, a difluoromethoxy group, a bromodifluoromethoxy group, a chlorodifluoromethoxy group, a fluoromethoxy group, a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, a 5-chloropentyloxy group, a 4-fluoroisopentyloxy group, a 2,2-dichlorohexyloxy group and the like;
the C3-C6 alkenyloxy group includes a 2-propenyloxy group, a 1-methyl-2-propenyloxy group, a 2-methyl-2-propenyloxy group, a 2-butenyloxy group, a 3-butenyloxy group, a 2-hexenyloxy group, a 5-hexenyloxy group and the like;
the C3-C6 haloalkenyloxy group includes a 3-chloro-2-propynyloxy group, a 3-bromo-2-propynyloxy group, a 3-iodo-2-propynyloxy group, a 6-chloro-5-hexenyloxy group and the like;
the C3-C6 alkynyloxy group includes a 2-propynyloxy group, a 1-methyl-2-propynyloxy group, a 2-butynyloxy group, a 3-butynyloxy group, a 2-hexynyloxy group, a 5-hexynyloxy group and the like;
the C3-C6 haloalkynyloxy group includes a 3-chloro-2-propynyloxy group, a 3-bromo-2-propynyloxy group, a 3-iodo-2-propynyloxy group, a 6-chloro-5-hexynyloxy group and the like;
the C2-C6 cyanoalkyloxy group includes a cyanomethyloxy group, a 1-cyanoethyloxy group, a 2-cyanoethyloxy group and the like;
the C1-C6 alkylthio group includes a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, an isobutylthio group, a sec-butylthio group, a
tert-butylthio group, a pentylthio group, an isopentylthio group, a hexylthio group and the like;
the C1-C6 haloalkylthio group includes a trifluoromethylthio group, a difluoromethylthio group, a bromodifluoromethylthio group, a chlorodifluoromethylthio group, a fluoromethylthio group, a 2,2,2-trifluoroethylthio group, a 1,1,2,2-tetrafluoroethylthio group, a 5-chloropentylthio group, a 4-f luoroisopentylthio group, a 2,2-dichlorohexylthio group and the like;
the C3-C6 cycloalkyl group includes a cyclopropyl group, a cyclopentyl group, a cyclohexyl group and the like; and
the C3-C6 cycloalkyloxy group includes a cyclopropyloxy group, a cyclopentyloxy group, a cyclohexyloxy group and the like.
In the representation of R21, R22, R23, R24, R25, R26, R27, R28,
R29, R30, R31 and R32, the halogen atom includes a fluorine atom,
a chlorine atom, a bromine atom and the like;
the C1-C3 alkyl group includes a methyl group, an ethyl group, a propyl group and the like;
the C1-C3 alkoxy group includes a methoxy group, an ethoxy group, a propoxy group and the like; and
the C1-C3 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chloromethyl group, a bromomethyl group, a 2,2,2-trifluoroethyl group, a trichloromethyl group and the like.
the C1-C3 alkyl group includes a methyl group, an ethyl group, a propyl group and the like;
the C1-C3 alkoxy group includes a methoxy group, an ethoxy group, a propoxy group and the like; and
the C1-C3 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chloromethyl group, a bromomethyl group, a 2,2,2-trifluoroethyl group, a trichloromethyl group and the like.
In the representation of R14, the C1-C3 alkyl group includes
a methyl group, an ethyl group, a propyl group and the like.
In the representation of R15, the C1-C6 alkyl group includes
a methyl group, an ethyl group, a propyl group, an isopropyl group,
a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl
group, a pentyl group, an isopentyl group, a hexyl group and the
like;
the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a trichloromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2, 2,2-trifluoroethyl group, a 6, 6, 6-trifluorohexyl group and the like;
the C3-C6 alkenyl group includes a 2-propenyl group, a 1-methyl-2-propenyl group, a 1,1-dimethyl-2-propenyl group, a 2-methyl-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 2-hexenyl group, a 5-hexenyl group and the like;
the C3-C6 haloalkenyl group includes a 3,3-dichloro-2-propenyl group, a 2,3-dichloro-2-propenyl group, a 3,3-difluoro-2-propenyl group and the like;
the C3-C6 alkynyl group includes a 2-propynyl group, a 1-methyl-2-propynyl group, a 1,1-dimethyl-2-propynyl group, a 2-butynyl group, a 3-butynyl group, a 2-hexynyl group, a 5-hexynyl group and the like;
the C3-C6 haloalkynyl group includes a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 6-chloro-5-hexynyl group and the like;
the C3-C6 cycloalkyl group includes a cyclopropyl group, a cyclopentyl group, a cyclohexyl group and the like;
the (C1-C6 alkyl)carbonyl group includes an acetyl group, an ethylcarbonyl group, a propylcarbonyl group, an isopropylcarbonyl group, a butylcarbonyl group, a isobutylcarbonyl group, a sec-butylcarbonyl group, a tert-butylcarbonyl group, a pentylcarbonyl group, an isopentylcarbonyl group, a hexylcarbonyl group and the like;
the (C1-C6 haloalkyl) carbonyl group includes a chloroacetyl group, a bromoacetyl group, a difluoroacetyl group, a trifluoroacetyl group, a trichloroacetyl group, a chlorofluoroacetyl group, a bromodifluoroacetyl group, a 2-fluoroethylcarbonyl group, a 2,2-difluoroethylcarbonyl group, a 2,2,2-trifluoroethylcarbonyl group, a 6,6,6-trifluorohexylcarbonyl group and the like;
the (C1-C6 alkoxy) carbonyl group includes a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isopropoxycarbonyl group, a butoxycarbonyl group, an isobutoxycarbonyl group, a sec-butoxycarbonyl group, a tert-butoxycarbonyl group, a pentyloxycarbonyl group, an isopentyloxycarbonyl group, a hexyloxycarbonyl group and the like;
the (C1-C6 haloalkoxy)carbonyl group includes a 2,2,2-trifluoroethoxycarbonyl group, a 1,1,2,2-tetrafluoroethoxycarbonyl group, a 5-chloropentyloxycarbonyl group, a 2,2-dichlorohexyloxycarbonyl group and the like;
the (C3-C6 alkenyloxy)carbonyl group includes a 2-propenyloxycarbonyl group, a 1-methyl-2-propenyloxycarbonyl group, a 2-methyl-2-propenyloxycarbonyl group, a 2-butenyloxycarbonyl group, a 3-butenyloxycarbonyl group, a 2-hexenyloxycarbonyl group, a 5-hexenyloxy group carbonyl and the like;
the (C3-C6 haloalkenyloxy)carbonyl group includes a 3-chloro-2-propynyloxycarbonyl group, a 3-bromo-2-propynyloxycarbonyl group, a 3-iodo-2-propynyloxycarbonyl group, a 6-chloro-5-hexenyloxycarbonyl group and the like;
the (C3-C6 alkynyloxy)carbonyl group includes a 2-propynyloxycarbonyl group, a 1-methyl-2-propynyloxycarbonyl group, a 2-butynyloxycarbonyl group, a 3-butynyloxycarbonyl group, a 2-hexynyloxycarbonyl group, a 5-hexynyloxycarbonyl group and the like;
the (C3-C6 haloalkynyloxy)carbonyl group includes a 3-chloro-2-propynyloxycarbonyl group, a 3-bromo-2-propynyloxycarbonyl group, a 3-iodo-2-propynyloxycarbonyl group, a 6-chloro-5-hexynyloxycarbonyl group and the like; and
the C1-C3 alkylsulfonyl group includes a methanesulfonyl group, an ethanesulfonyl group, or the like.
the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a trichloromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2, 2,2-trifluoroethyl group, a 6, 6, 6-trifluorohexyl group and the like;
the C3-C6 alkenyl group includes a 2-propenyl group, a 1-methyl-2-propenyl group, a 1,1-dimethyl-2-propenyl group, a 2-methyl-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 2-hexenyl group, a 5-hexenyl group and the like;
the C3-C6 haloalkenyl group includes a 3,3-dichloro-2-propenyl group, a 2,3-dichloro-2-propenyl group, a 3,3-difluoro-2-propenyl group and the like;
the C3-C6 alkynyl group includes a 2-propynyl group, a 1-methyl-2-propynyl group, a 1,1-dimethyl-2-propynyl group, a 2-butynyl group, a 3-butynyl group, a 2-hexynyl group, a 5-hexynyl group and the like;
the C3-C6 haloalkynyl group includes a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 6-chloro-5-hexynyl group and the like;
the C3-C6 cycloalkyl group includes a cyclopropyl group, a cyclopentyl group, a cyclohexyl group and the like;
the (C1-C6 alkyl)carbonyl group includes an acetyl group, an ethylcarbonyl group, a propylcarbonyl group, an isopropylcarbonyl group, a butylcarbonyl group, a isobutylcarbonyl group, a sec-butylcarbonyl group, a tert-butylcarbonyl group, a pentylcarbonyl group, an isopentylcarbonyl group, a hexylcarbonyl group and the like;
the (C1-C6 haloalkyl) carbonyl group includes a chloroacetyl group, a bromoacetyl group, a difluoroacetyl group, a trifluoroacetyl group, a trichloroacetyl group, a chlorofluoroacetyl group, a bromodifluoroacetyl group, a 2-fluoroethylcarbonyl group, a 2,2-difluoroethylcarbonyl group, a 2,2,2-trifluoroethylcarbonyl group, a 6,6,6-trifluorohexylcarbonyl group and the like;
the (C1-C6 alkoxy) carbonyl group includes a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isopropoxycarbonyl group, a butoxycarbonyl group, an isobutoxycarbonyl group, a sec-butoxycarbonyl group, a tert-butoxycarbonyl group, a pentyloxycarbonyl group, an isopentyloxycarbonyl group, a hexyloxycarbonyl group and the like;
the (C1-C6 haloalkoxy)carbonyl group includes a 2,2,2-trifluoroethoxycarbonyl group, a 1,1,2,2-tetrafluoroethoxycarbonyl group, a 5-chloropentyloxycarbonyl group, a 2,2-dichlorohexyloxycarbonyl group and the like;
the (C3-C6 alkenyloxy)carbonyl group includes a 2-propenyloxycarbonyl group, a 1-methyl-2-propenyloxycarbonyl group, a 2-methyl-2-propenyloxycarbonyl group, a 2-butenyloxycarbonyl group, a 3-butenyloxycarbonyl group, a 2-hexenyloxycarbonyl group, a 5-hexenyloxy group carbonyl and the like;
the (C3-C6 haloalkenyloxy)carbonyl group includes a 3-chloro-2-propynyloxycarbonyl group, a 3-bromo-2-propynyloxycarbonyl group, a 3-iodo-2-propynyloxycarbonyl group, a 6-chloro-5-hexenyloxycarbonyl group and the like;
the (C3-C6 alkynyloxy)carbonyl group includes a 2-propynyloxycarbonyl group, a 1-methyl-2-propynyloxycarbonyl group, a 2-butynyloxycarbonyl group, a 3-butynyloxycarbonyl group, a 2-hexynyloxycarbonyl group, a 5-hexynyloxycarbonyl group and the like;
the (C3-C6 haloalkynyloxy)carbonyl group includes a 3-chloro-2-propynyloxycarbonyl group, a 3-bromo-2-propynyloxycarbonyl group, a 3-iodo-2-propynyloxycarbonyl group, a 6-chloro-5-hexynyloxycarbonyl group and the like; and
the C1-C3 alkylsulfonyl group includes a methanesulfonyl group, an ethanesulfonyl group, or the like.
In the representation of R16, the C1-C6 alkyl group includes
a methyl group, an ethyl group, a propyl group, an isopropyl group,
a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl
group, a pentyl group, an isopentyl group, a hexyl group and the
like;
the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, a 2, 2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6, 6, 6-trif luorohexyl group and the like;
the C3-C6 alkenyl group includes a 2-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 2-hexenyl group, a 5-hexenyl group and the like;
the C3-C6 haloalkenyl group includes a 2,3-dichloropropenyl group, a 3,3-dichloropropenyl group, a 3,3-difluoropropenyl group and the like;
the C3-C6 alkynyl group includes a 2-propynyl group, a 1-methyl-2-propynyl group, a 1,1-dimethyl-2-propynyl group, a 2-butynyl group, a 3-butynyl group, a 2-hexynyl group, a 5-hexynyl group and the like;
the C3-C6 haloalkynyl group includes a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 6-chloro-5-hexynyl group and the like; and
the C3-C6 cycloalkyl group includes a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group and the like.
the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, a 2, 2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6, 6, 6-trif luorohexyl group and the like;
the C3-C6 alkenyl group includes a 2-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 2-hexenyl group, a 5-hexenyl group and the like;
the C3-C6 haloalkenyl group includes a 2,3-dichloropropenyl group, a 3,3-dichloropropenyl group, a 3,3-difluoropropenyl group and the like;
the C3-C6 alkynyl group includes a 2-propynyl group, a 1-methyl-2-propynyl group, a 1,1-dimethyl-2-propynyl group, a 2-butynyl group, a 3-butynyl group, a 2-hexynyl group, a 5-hexynyl group and the like;
the C3-C6 haloalkynyl group includes a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 6-chloro-5-hexynyl group and the like; and
the C3-C6 cycloalkyl group includes a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group and the like.
In the representation of R17, the halogen atom includes a
fluorine atom, a chlorine atom, a bromine atom and the like;
the C1-C6 alkyl group includes a methyl group, an ethyl group,
a propyl group, an isopropyl group, a butyl group, an isobutyl
group, a sec-butyl group, a tert-butyl group, a pentyl group, an
isopentyl group, a hexyl group and the like;
the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6,6,6-trifluorohexyl group and the like;
the C1-C6 alkoxy group includes a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, an isopentyloxy group, a hexyloxy group and the like;
the C1-C6 haloalkoxy group includes a trifluoromethoxy group, a difluoromethoxy group, a bromodifluoromethoxy group, a chlorodifluoromethoxy group, a fluoromethoxy group, a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, a 5-chloropentyloxy group, a 4-fluoroisopentyloxy group, a 2,2-dichlorohexyloxy group and the like;
the C3-C6 alkenyloxy group includes a 2-propenyloxy group, a 1-methyl-2-propenyloxy group, a 2-methyl-2-propenyloxy group, a 2-butenyloxy group, a 3-butenyloxy group, a 2-hexenyloxy group, a 5-hexenyloxy group and the like;
the C3-C6 haloalkenyloxy group includes a 3, 3-dichloro-2-propynyloxy group, a 3-chloro-2-propynyloxy group, a 3-bromo-2-propynyloxy group, a 3-iodo-2-propynyloxy group, a 6-chloro-5-hexenyloxy group and the like;
the C3-C6 alkynyloxy group includes a 2-propynyloxy group, a 1-methyl-2-propynyloxy group, a 2-butynyloxy group, a 3-butynyloxy group, a 2-hexynyloxy group, a 5-hexynyloxy group and the like; and
the C3-C6 haloalkynyloxy group includes a 3-chloro-2-propynyloxy group, a 3-bromo-2-propynyloxy group, a 3-iodo-2-propynyloxy group, a 6-chloro-5-hexynyloxy group and the like;
the C3-C6 cycloalkyloxy group includes a cyclopropyloxy group, a cyclobutyloxy group, a cyclopentyloxy group, a cyclohexyloxy group and the like.
the C1-C6 haloalkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6,6,6-trifluorohexyl group and the like;
the C1-C6 alkoxy group includes a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, an isopentyloxy group, a hexyloxy group and the like;
the C1-C6 haloalkoxy group includes a trifluoromethoxy group, a difluoromethoxy group, a bromodifluoromethoxy group, a chlorodifluoromethoxy group, a fluoromethoxy group, a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, a 5-chloropentyloxy group, a 4-fluoroisopentyloxy group, a 2,2-dichlorohexyloxy group and the like;
the C3-C6 alkenyloxy group includes a 2-propenyloxy group, a 1-methyl-2-propenyloxy group, a 2-methyl-2-propenyloxy group, a 2-butenyloxy group, a 3-butenyloxy group, a 2-hexenyloxy group, a 5-hexenyloxy group and the like;
the C3-C6 haloalkenyloxy group includes a 3, 3-dichloro-2-propynyloxy group, a 3-chloro-2-propynyloxy group, a 3-bromo-2-propynyloxy group, a 3-iodo-2-propynyloxy group, a 6-chloro-5-hexenyloxy group and the like;
the C3-C6 alkynyloxy group includes a 2-propynyloxy group, a 1-methyl-2-propynyloxy group, a 2-butynyloxy group, a 3-butynyloxy group, a 2-hexynyloxy group, a 5-hexynyloxy group and the like; and
the C3-C6 haloalkynyloxy group includes a 3-chloro-2-propynyloxy group, a 3-bromo-2-propynyloxy group, a 3-iodo-2-propynyloxy group, a 6-chloro-5-hexynyloxy group and the like;
the C3-C6 cycloalkyloxy group includes a cyclopropyloxy group, a cyclobutyloxy group, a cyclopentyloxy group, a cyclohexyloxy group and the like.
In the representation of R18, the halogen atom includes a
fluorine atom, a chlorine atom, a bromine atom and the like;
the C1-C6 alkyl group includes a methyl group, an ethyl group,
a propyl group, an isopropyl group, a butyl group, a isobutyl group,
a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl
group, a hexyl group and the like; and
the C1-C6 haloalkyl group includes a trifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6,6,6-trifluorohexyl group and the like.
the C1-C6 haloalkyl group includes a trifluoromethyl group, a chlorofluoromethyl group, a bromodifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6,6,6-trifluorohexyl group and the like.
In the representation of R19 and R20, the C1-C6 alkyl group
includes a methyl group, an ethyl group, a propyl group, an isopropyl
group, a butyl group, an isobutyl group, a sec-butyl group, a
tert-butyl group, a pentyl group, an isopentyl group, a hexyl group
and the like;
the C1-C6 haloalkyl group includes a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6,6,6-trifluorohexyl group and the like;
the C3-C6 alkenyl group includes a 2-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 2-hexenyl group, a 5-hexenyl group and the like;
the C3-C6 haloalkenyl group includes a 3,3-dichloro-2-propynyl group, a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 3-iodo-2-propynyl group, a 6-chloro-5-hexenyl group and the like; the C3-C6 alkynyl group includes a 2-propynyl group, a 1-methyl-2-propynyl group, a 2-butynyl group, a 3-butynyl group, a 2-hexynyl group, a 5-hexynyl group and the like; and
the C3-C6 cycloalkyl group includes a cyclopropyl group, a cyclopentyl group, a cyclohexyl group and the like.
the C1-C6 haloalkyl group includes a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 6,6,6-trifluorohexyl group and the like;
the C3-C6 alkenyl group includes a 2-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 2-hexenyl group, a 5-hexenyl group and the like;
the C3-C6 haloalkenyl group includes a 3,3-dichloro-2-propynyl group, a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 3-iodo-2-propynyl group, a 6-chloro-5-hexenyl group and the like; the C3-C6 alkynyl group includes a 2-propynyl group, a 1-methyl-2-propynyl group, a 2-butynyl group, a 3-butynyl group, a 2-hexynyl group, a 5-hexynyl group and the like; and
the C3-C6 cycloalkyl group includes a cyclopropyl group, a cyclopentyl group, a cyclohexyl group and the like.
The embodiment of the compound of the present invention
includes, for example, the following compounds:
Methods for producing the compounds of the present invention
are described hereinafter.
The compound of the present invention can be produced, for
example, according to the following (Production Method 1) to
(Production Method 12). In these production methods, protecting
groups may be, if necessary, applied to protect functional groups
from chemical reactions.
The compound (4) among the compounds of the present invention
can be produced by subjecting the compound (2) to reaction with
the compound (3);
(, wherein, in the formula, L1 represents a chlorine atom or a bromine
atom, R1, R2, R3, R4, R5, R7, R8, R9, R10, R11, W1―W2=W3―W4 and Q represent
same meaning defined in [Invention 1].)
Said reaction is carried out in the presence of a base and
usually in a solvent.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
such as chlorobenzene and the like; esters such as butylacetate,
ethylacetate and the like; organic nitriles such as acetonitrile
and the like; acid amides such as N,N-dimethylformamide and the
like; sulfoxides such as dimethylsulfoxide and the like; and the
mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; alkali metal
hydrides such as sodium hydride and the like; tertiary amines such
as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar ratio applied to the compound (3) is usually from
0.5 to 2 moles per 1 mole of the compound (2) and that to the base
is 10 moles or less.
The reaction time is usually in the range of from 0.1 to
24 hours, and the reaction temperature is in the range of from
0 to 150 °C.
After completion of the reaction, the compound (4) can be
isolated by being subjectedtopost treatment procedure exemplified
below.
The compound (6) among the compounds of the present invention
can be produced by subjecting the compound (5) to reaction with
2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-dis
ulfide (,which is referred to as "Lawesson's reagent" hereinafter);
(, wherein, in the formula, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10,
R11, W1―W2=W3―W4 and Q represent same meaning defined in [Invention
1].)
Said reaction is usually carried out in a solvent.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
t-butylmethylethers and the like; aliphatic hydrocarbons such as
hexane, heptane and the like; aromatic hydrocarbons such as toluene,
xylene and the like; halogenated hydrocarbons such as chlorobenzene
and the like; organic nitriles such as acetonitrile, butyronitrile
and the like; sulfoxides such as dimethylsulfoxide and the like;
and the mixture thereof.
Lawesson's reagent is usually used in the molar ratio of
from 1 to 10 moles per 1 mole of the compound (5).
The reaction time is usually in the range of from 0.5 to
24 hours, and the reaction temperature is in the range of from
30 to 150 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (6). The isolated compound (6) can
be purified by a technique such as chromatography,
recrystallization and the like.
The compound (9) among the compounds of the present invention
can be produced by subjecting the compound (7) to reaction with
the compound (8);
(, wherein, in the formula, L2 represents a bromine atom, an iodine
atom or a methanesulfonyloxy group, R6-1 represents a C1-C3 alkyl
group, R1, R2, R3, R4, R5, R7, R8, R9, R10, R11, W1―W2=W3―W4 and Q
represent same meaning defined in [Invention 1], and X represents
same meaning described above.)
Said reaction is carried out in the presence of a base and
usually in a solvent.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
chlorobenzene and the like; esters such as butylacetate,
ethylacetate and the like; organic nitriles such as acetonitrile
and the like; acid amides such as N,N-dimethylformamide and the
like; sulfoxides such as dimethylsulfoxide and the like; and the
mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; alkali metal
hydrides such as sodium hydride and the like; and tertiary amines
such as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like.
The molar ratio applied to the compound (8) is usually from
1 to 10 moles per 1 mole of the compound (7) and that to the base
is usually from 1 to 10 moles.
The reaction time is usually in the range of from 0.5 to
24 hours, and the reaction temperature is in the range of from
0 to 120 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (9). The isolated compound (9) can
be purified by a technique such as chromatography,
recrystallization and the like.
The compound (11) among the compounds of the present invention
can be produced by subjecting the compound (10) to reaction with
a reducing agent;
(, wherein, in the formula, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10,
R11 and W1―W2=W3―W4 represent same meaning defined in [Invention
1], and X represents same meaning described above.)
Said reaction is usually carried out in a solvent.
The reducing agent used for the reaction includes sodium
borohydride or potassium borohydride.
The solvent used for the reaction includes alcohols such
as methanol, ethanol, 2-propanol and the like; ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; and water and the mixture
thereof.
The molar ratio applied to the reducing agent is usually
from 0.25 to 3 moles per 1 mole of the compound (10).
The reaction time is usually in the range of from the instant
to 24 hours, and the reaction temperature is in the range of from
-20 to 100 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as, after being added
with an acidic water such as aqueous saturated ammonium chloride,
extracting with organic solvent, subsequently drying and
concentrating the organic layer obtained, to isolate the compound
(11). The isolated compound (11) can be purified by a technique
such as chromatography, recrystallization and the like.
The compound (12) among the compounds of the present invention
can be produced by subjecting the compound (10) to reaction with
organic metal compounds such as alkylmagnesium halide (Grignard
reagent), alkyllithium and the like which correspond to R14-1;
(, wherein, in the formula, R14-1 represents a C1-C3 alkyl group,
R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and W1―W 2=W3―W4 represent
same meaning defined in [Invention 1], and X represents same meaning
described above.)
Said reaction is usually carried out in a solvent.
The organic metal compound corresponding to R14-1 used in the
reaction is defined by an organic metal compound in which R14-1 is
the organic group coupled with a metal element, and is illustrated
by alkylmagnesium halide and alkyllithium. Specifically included
are methylmagnesiumbromide, methyllithium,
ethylmagnesiumchloride and ethyllithium.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; and aromatic hydrocarbons
such as toluene, xylene and the like.
The molar range applied to the organic metal compound is
usually from 1 to 3 moles per 1 mole of the compound (10).
The reaction time is usually in the range of from the instant
to 24 hours, and the reaction temperature is in the range of from
-80 to 50 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (12). The isolated compound (12)
can be purified by a technique such as chromatography,
recrystallization and the like.
The compound (14) and the compound (16) among the compounds
of the present invention can be produced by the following method.
That is, the compound (14) can be produced by subj ecting the compound
(13) to reaction with an alkylsulfonyl chloride compound (Step
6-1), and furthermore, the compound (16) can be produced by
subjecting the compound (14) to reaction with the compound (15)
(, wherein, in the formula, R33 represents a C1-C3 alkyl group,
R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R14, R15 and W1―W2=W3
-W4 represent same meaning defined in [Invention 1], and X and
Z1 represent same meaning described above.)
Said reaction is carried out in the presence of a base and
usually in a solvent.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
such as chlorobenzene and the like; esters such as butylacetate,
ethylacetate and the like; organic nitriles such as acetonitrile
and the like; acid amides such as N,N-dimethylformamide and the
like; sulfoxides such as dimethylsulfoxide and the like; and the
mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; alkali metal
hydrides such as sodium hydride and the like; tertiary amines such
as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar ratio applied to the alkylsulfonyl chloride
compound is usually from 1 to 3 moles per 1 mole of the compound
(13) and that to the base is usually from 1 to 10 moles.
The reaction time is usually in the range of from 0.1 to
24 hours, and the reaction temperature is in the range of from
-20 to 100 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, if necessary, after the organic layer being washed
by acidic water, basic water or the like, subsequently drying and
concentrating the organic layer, to isolate the compound (14).
The isolated compound (14) can be purified by a technique such
as recrystallization and the like.
Said reaction is carried out with or without the presence
of a solvent with or without the presence of a base.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
such as chlorobenzene and the like; esters such as butylacetate,
ethylacetate and the like; organic nitriles such as acetonitrile
and the like; acid amides such as N,N-dimethylformamide and the
like; sulfoxides such as dimethylsulfoxide and the like; and the
mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; alkali metal
hydrides such as sodium hydride and the like; tertiary amines such
as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar ratio applied to the compound (15) is usually from
1 mole to excessive amount per 1 mole of the compound (14).
The reaction time is usually in the range of from 0.5 to 24 hours,
and the reaction temperature is in the range of from 0 to 150 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, if necessary, after the organic layer being washed
by acidic water, basic water or the like, subsequently drying and
concentrating the organic layer, to isolate the compound (16).
The isolated compound (16) can be purified by a technique such
as recrystallization and the like.
The compound (19) among the compounds of the present invention
can be produced by subjecting the compound (17) to reaction with
the compound (18) or the salt thereof;
(, wherein, in the formula, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10,
R11, R16 and W1―W2=W3―W4 represent same meaning defined in [Invention
1], and X represents same meaning described above.)
Said reaction is usually carried out in a solvent, and if
necessary, in the presence of a base.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
such as chlorobenzene and the like; esters such as butylacetate,
ethylacetate and the like; alcohols such as methanol, ethanol,
propanol and the like; organic nitriles such as acetonitrile and
the like; acid amides such as N,N-dimethylformamide and the like;
sulfoxides such as dimethylsulfoxide and the like; and the mixture
thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate, sodium bicarbonate and the
like; tertiary amines such as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar range applied to the base is usually from the
catalytic amount to 10 moles per 1 mole of the compound (17) and
that to the compound (18) or the salt thereof is usually from 1
to 10 moles.
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from 0 to
150 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, and if necessary, after the organic layer being
washed by acidic water, and subsequently drying and concentrating
the organic layer, to isolate the compound (19). The isolated
compound (19) can be purified by a technique such as chromatography,
recrystallization and the like.
The compound (22) among the compounds of the present invention
can be produced by subjecting the compound (20) to reaction with
the compound (21):
(, wherein, in the formula, L3 represents a chlorine atom, a bromine
atom and a methanesulfonyloxy group; R15-1 represents a C1-C6 alkyl
group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6
haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group,
a C3-C6 cycloalkyl group, a (C1-C6 alkyl) carbonyl group, a (C1-C6
haloalkyl) carbonyl group, a (C1-C6 alkoxy) carbonyl group, a (C1-C6
haloalkoxy)carbonyl group, a (C3-C6 alkenyloxy)carbonyl group,
a (C3-C6 haloalkenyloxy)carbonyl group, a (C3-C6
alkynyloxy) carbonyl group, a (C3-C6 haloalkynyloxy) carbonyl group
or a C1-C3 alkylsulfonyl group; R1, R2, R3, R4, R5, R6, R7, R8, R9,
R10, R11, R14, W1―W2=W3―W4 and X represent same meaning defined in
[Invention 1]; and Z1 represents same meaning described above.)
Said reaction is usually carried out in a solvent with the
presence of a base.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
such as chlorobenzene and the like; esters such as butylacetate,
ethylacetate and the like; organic nitriles such as acetonitrile
and the like; acid amides such as N,N-dimethylformamide and the
like; sulfoxides such as dimethylsulfoxide and the like; and water
and the mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; alkali metal
hydrides such as sodium hydride and the like; tertiary amines such
as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar range applied to the compound (21) is usually from
1 to 3 moles per 1 mole of the compound (20) and that to the base
is usually from 1 to 3 moles.
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from 0 to
150 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (22). The isolated compound (22)
can be purified by a technique such as chromatography,
recrystallization and the like.
The compound (28) among the compounds of the present invention
can be produced by subjecting the compound (26) to reaction with
the compound (27);
(, wherein, in the formula, L5 represents a chlorine atom, a bromine
atom or an iodine atom, and R1, R2, R3, R4, R5, R7, R8, R9, R10, R11
and W1―W2=W3―W4 represent same meaning defined in [Invention 1].)
Said reaction is carried out in a solvent with the presence
of a catalyst.
The solvent used for the reaction includes alcohols such
as methanol, ethanol, propanol, butanol, 2-propanoland and the
like; ethers such as 1,4-dioxane, tetrahydrofuran,
ethyleneglycoldimethylether, tert-butylmethylether and the like;
aliphatic hydrocarbons such as hexane, heptane, octane and the
like; aromatic hydrocarbons such as toluene, xylene and the like;
water and the mixture thereof.
The catalyst used for the reaction includes palladium acetate,
tetrakistriphenylphosphine palladium,
{1,1'-bis(diphenylphosphino)ferrocene}dichloropalladium
methylene chloride complex and bis (triphenylphosphine) palladium
dichloride.
The molar range applied to the compound (27) is usually from
1 to 5 moles per 1 mole of the compound (26) and that to the catalyst
is usually from 0.001 to 0.1 moles.
Said reaction maybe, if necessary, carried out in the presence
of a base (, which includes inorganic base such as sodium acetate,
potassium acetate, potassium carbonate, tripotassium phosphate,
sodium bicarbonate and the like) and/or a phase-transfer catalyst
(, which includes quaternary ammonium salts such as
tetrabutylammonium bromide, benzyltriethylammonium bromide and
the like).
The reaction time is usually in the range of from 0.5 to
24 hours, and the reaction temperature is in the range of from
50 to 120 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as filtrating as itself,
subsequently concentrating the filtrate, to isolate the compound
(28). The isolated compound (28) can be purified by a technique
such as chromatography, recrystallization and the like.
The compound (42) among the compounds of the present invention
can be produced by subjecting the compound (40) to reaction with
the compound (41):
(, wherein, in the formula, L9 represents a chlorine atom, a bromine
atom and a methanesulfonyloxy group; R16-1 represents a C1-C6 alkyl
group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6
haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group
or a C3-C6 cycloalkyl group; R1, R2, R3, R4, R5, R6, R7, R8, R9, R10,
R11 and W1―W2=W3―W4 represent same meaning defined in [Invention
1]; and X represents same meaning described above.)
Said reaction is usually carried out in a solvent with the
presence of a base.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
chlorobenzene and the like; esters such as butylacetate,
ethylacetate and the like; organic nitriles such as acetonitrile
and the like; acid amides such as N,N-dimethylformamide and the
like; sulfoxides such as dimethylsulfoxide and the like; and the
mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; and alkali
metal hydrides such as sodium hydride and the like.
The molar range applied to the compound (41) is usually from
1 to 3 moles per 1 mole of the compound (40) and that to the base
is usually from 1 to 10 moles.
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from 0 to
150 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (42). The isolated compound (42)
can be purified by a technique such as chromatography,
recrystallization and the like.
The compound (45) among the compounds of the present invention
can be produced by subjecting the compound (43) to reaction with
the compound (44) :
[, wherein, in the formula, L10 represents leaving groups such as
a chlorine atom, a bromine atom, an iodine atom,
p-toluenesulfonyloxy group, a methanesulfonyloxy group and the
like; R34 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group,
a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl
group, a C3-C6 haloalkynyl group or a C3-C6 cycloalkyl group; R1,
R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and W1―W2=W3―W4 represent
same meaning defined in [Invention 1]; and X represents same meaning
described above.)
Said reaction is usually carried out in a solvent with the
presence of a base.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like;
aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as butylacetate, ethylacetate and the like; organic nitriles such as acetonitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; alkali metal
hydrides such as sodium hydride and the like; tertiary amines such
as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar range applied to the compound (44) is usually from
1 to 3 moles per 1 mole of the compound (43) and that to the base
is usually from 1 to 5 moles.
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from 0 to
150 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (45). The isolated compound (45)
can be purified by a technique such as chromatography,
recrystallization and the like.
The compound (52) among the compounds of the present invention
can be produced by subjecting the compound (25) to reaction with
the compound (18) or the salt thereof to obtain the compound (51)
(Step 12-1), and then subjecting the compound (51) to reaction
with the compound (27) (Step 12-2);
(, wherein, in the formula, R1, R2, R3, R4, R5, R7, R8, R9, R10, R11
and W1―W2=W3―W4 represent same meaning defined in [Invention 1],
and R16 and L5 represent same meaning described above.)
Said reaction is usually carried out in a solvent, and if
necessary, in the presence of a base.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
such as chlorobenzene and the like; esters butylacetate,
ethylacetate and the like; alcohols such as methanol, ethanol,
propanol and the like; organic nitriles such as acetonitrile and
the like; acid amides such as N,N-dimethylformamide and the like;
sulfoxides such as dimethylsulfoxide and the like; and the mixture
thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate, sodium bicarbonate and the
like; tertiary amines such as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar range applied to the base is usually from the
catalytic amount to 10 moles per 1 mole of the compound (25) and
that to the compound (18) or the salt thereof is usually from 1
to 10 moles.
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from 0 to
150 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, and if necessary, the organic layer being washed
by acidic water and the like, subsequently drying and concentrating
the organic layer, to isolate the compound (51). The isolated
compound (51) can be purified by a technique such as chromatography,
recrystallization and the like.
Said reaction is carried out in a solvent with the presence
of a catalyst.
The solvent used for the reaction includes alcohols such
as methanol, ethanol, propanol, butanol, 2-propanol and the like;
ethers such as 1,4-dioxane, tetrahydrofuran,
ethyleneglycoldimethylether, tert-butylmethylether and the like;
aliphatic hydrocarbons such as hexane, heptane, octane and the
like; aromatic hydrocarbons such as toluene, xylene and the like;
water and the mixture thereof.
The catalyst used for the reaction includes palladium acetate,
tetrakistriphenylphosphine palladium,
{1,1'-bis(diphenylphosphino)ferrocene}dichloropalladium
methylene chloride complex and bis (triphenylphosphine) palladium
dichloride.
The molar range applied to the compound (27) is usually from
1 to 5 moles per 1 mole of the compound (51) and that to the catalyst
is usually from 0.001 to 0.1 moles.
Said reaction may be, if necessary, carried out in the presence
of a base (, which includes inorganic base such as sodium acetate,
potassium acetate, potassium carbonate, tripotassium phosphate,
sodium bicarbonate and the like) and/or a phase-transfer catalyst
(, which includes quaternary ammonium salts such as
tetrabutylammonium bromide, benzyltriethylammonium bromide and
the like).
The reaction time is usually in the range of from 0.5 to
24 hours, and the reaction temperature is in the range of from
50 to 120 °C.
After completion of the reaction, the compound (52) can be
isolated by being subjected to post treatment procedure exemplified
below.
The isolated compound (52) can be purified by technique such
as chromatography, recrystallization and the like.
Next, methods for producing intermediate compounds of the
compound of the present invention are described as follows.
The compound (3) can be produced, for example, according
to the following (Intermediate Compound Production Method 1) or
(Intermediate Compound Production Method 2).
(, wherein, in the formula, L6 represents a chlorine atom, a bromine
atom and an iodine atom; and R7, R8, R9, R10, R11 and W1―W2=W3―
W4 represent same meaning defined in [Invention 1].)
The compound (30) can be produced by subjecting the compound
(29) to reaction with the compound (27).
Said reaction is carried out in a solvent with the presence
of a catalyst.
The solvent used for the reaction includes, alcohols such
as methanol, ethanol, propanol, butanol, 2-propanoland and the
like; ethers such as 1,4-dioxane, tetrahydrofuran,
ethyleneglycoldimethylether, tert-butylmethylether and the like;
aliphatic hydrocarbons such as hexane, heptane, octane and the
like; aromatic hydrocarbons such as toluene, xylene and the like;
water and the mixture thereof.
The catalyst used for the reaction includes palladium acetate,
tetrakistriphenylphosphine palladium, {1,1'
-bis(diphenylphosphino)ferrocene}dichloropalladium methylene
chloride complex and bis(triphenylphosphine) palladium
dichloride.
The molar ratio applied to the compound (27) is usually from
1 to 5 moles per 1 mole of the compound (29) and that to the catalyst
is usually from 0.001 to 0.1 moles.
Saidreactionmaybe, if necessary, carried out in the presence
of a base (, which includes inorganic base such as sodium acetate,
potassium acetate, potassium carbonate, tripotassium phosphate,
sodium bicarbonate and the like) and/or a phase-transfer catalyst
(, which includes quaternary ammonium salts such as
tetrabutylammonium bromide, benzyltriethylammonium bromide and
the like).
The reaction time is usually in the range of from 0.5 to
24 hours, and the reaction temperature is in the range of from
50 to 120 °C.
After completion of the reaction, the compound (30) can be
isolated by being subjected to post treatment procedure exemplified
below.
The isolated compound (30) can be purified by a technique
chromatography, recrystallization and the like.
The compound (3) can be produced by subjecting the compound
(30) to reduction reaction.
Said reduction reaction includes a method to reduce the
compound (30) by hydrogen in the presence of hydrogenation catalyst
(, said method is referred to as (Step I-2-1) hereinafter), and
a method to reduce the compound (30) by iron in the presence of
an acidic water (, said method is referred to as (Step I-2-2)
hereinafter).
The reaction of this step is usually carried out in a solvent.
The solvent used for the reaction of the present step includes
alcohols such as methanol, ethanol and the like; and ethers such
as 1,4-dioxane, tetrahydrofuran and the like.
The hydrogenation catalyst used for the reaction includes
palladium catalysts such as palladium-carbon and platinum catalysts
such as platinum-carbon.
The molar ratio applied to hydrogen is usually from 3 to
10 moles per 1 mole of the compound (30) and that to the catalyst
is usually from 0.001 to 0.1 moles.
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from 20
to 50 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as filtrating,
subsequently concentrating the filtrate, to isolate the compound
(3). The isolated compound (3) can be purified by a technique such
as chromatography, recrystallization and the like.
The acidic waters used for the reaction in this step include
aqueous acetic acid, diluted hydrochloric acid, aqueous sulfuric
acid and the like. The reaction may be, if necessary, carried out
in the presence of esters such as ethylacetate and the like; and
ethers such as tetrahydrofuran and the like. The iron used for
the reaction is usually used in the form of powder.
The molar ratio applied to the iron is usually from 6 to
30 moles per 1 mole of the compound (30).
The reaction time is usually in the range of from 0.1 to
10 hours, and the reaction temperature is in the range of from
40 to 100 °C.
After completion of the reaction, the reaction mixture is
subjected to filtration, the filtrate obtained being washed by
a basic water (such as aqueous saturated sodium bicarbonate and
the like) and then being subjected to extraction with organic solvent,
subsequently drying and concentrating the organic layer, to isolate
the compound (3). The isolated compound (3) can be purified by
a technique such as chromatography, recrystallization and the like.
(, wherein, in the formula, L7 represents a chlorine atom, a bromine
atom and an iodine atom, L8 represents a C1-C5 alkylcarbonyl group
(an acetyl group, a pivaloyl group and the like) , and R7, R8, R9,
R10, R11 and W1―W2=W3―W4 represent same meaning defined in [Invention
1].)
The compound (32) can be produced by subjecting the compound
(31) to reaction with the compound (27).
Said reaction is carried out in a solvent with the presence
of a catalyst.
The solvent used for the reaction includes alcohols such
as methanol, ethanol, propanol, butanol, 2-propanol and the like;
ethers such as 1,4-dioxane, tetrahydrofuran,
ethyleneglycoldimethylether, tert-butylmethylether and the like;
aliphatic hydrocarbons such as hexane, heptane, octane and the
like; aromatic hydrocarbons such as toluene, xylene and the like;
and water and the mixture thereof.
The catalyst used for the reaction includes palladium acetate,
tetrakistriphenylphosphine palladium, {1,1'
-bis(diphenylphosphino)ferrocene}dichloropalladium methylene
chloride complex and bis(triphenylphosphine) palladium
dichloride.
The molar ratio applied to the compound (27) is usually from
1 to 5 moles per 1 mole of the compound (31) and that to the catalyst
is usually from 0.001 to 0.1 moles.
Said reaction maybe, if necessary, carried out in the presence
of a base (, which includes inorganic base such as sodium acetate,
potassium acetate, potassium carbonate, tripotassium phosphate,
sodium bicarbonate and the like) and/or a phase-transfer catalyst
(, which includes quaternary ammonium salts such as
tetrabutylammonium bromide, benzyltriethylammonium bromide and
the like).
The reaction time is usually in the range of from 0.5 to
24 hours, and the reaction temperature is in the range of from
50 to 120 °C.
After completion of the reaction, the compound (32) can be
isolated by being subjected to post treatment procedure exemplified
below.
The compound (3) can be produced by subjecting the compound
(32) tohydrolysis in the presence of abase (suchassodiumhydroxide,
potassium hydroxide and the like).
The reaction is carried out in a solvent.
The solvent used for the reaction includes mixtures with
water and alcohols such as methanol, ethanol and the like or ethers
such as 1,4-dioxane and the like.
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from 20
to 100 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (3). The isolated compound (3) can
be purified by a technique such as chromatography,
recrystallization and the like.
The compound (2) can be produced according to the
(Intermediate Compound Production Method 3). That is, the compound
(2) can be produced by subjecting the compound (34) to reaction
with a halogenating agent (such as thionyl chloride, thionyl bromide
and the like).
(, wherein, in the formula, L1 represents a chlorine atom or a bromine
atom; and R1, R2, R3, R4, R5 and Q represent same meaning defined
in [Invention 1].)
Said reaction is usually carried out in a solvent.
The solvent used for the reaction includes aromatic
hydrocarbons such as toluene, xylene and the like.
The molar ratio applied to the halogenating agent is usually
from 1 to 5 moles per 1 mole of the compound (34).
The reaction time is usually in the range of from 0.5 to
24 hours, and the reaction temperature is in the range of from
50 to 120 °C.
After completion of the reaction, the compound (2) can be
isolated from the reaction mixture by being subjected to post
treatment procedure such as concentration and the like.
Some of the compound (34) can be produced according to the
methods described in International Publication WO01/95721,
International Publication WO00/41998, International Publication
WO96/23763 or International Publication WO96/31464.
Furthermore, the compound (50) among the compound (34) can
be produced according to (Intermediate Compound Production Method
4).
(, wherein, in the formula, R1, R2, R3, R4 and R5 represent same
meaning defined in [Invention 1] and R15 represents same meaning
described above.)
The compound (36) can be produced by subjecting the compound
(35) to react with a reducing agent.
Said reaction is carried out in a solvent.
The reducing agent used for the reaction includes sodium
borohydride and potassium borohydride.
The solvent used for the reaction includes alcohols such
as methanol, ethanol, 2-propanol and the like; ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like ; aromatic hydrocarbons such
as toluene, xylene and the like ; and water and the mixture thereof.
The molar ratio applied to the reducing agent is usually
from 0.25 to 3 moles per 1 mole of the compound (35).
The reaction time is usually in the range of from the instant
to 24 hours, and the reaction temperature is in the range of from
-20 to 100 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (36). The isolated compound (36)
can be purified by a technique such as chromatography,
recrystallization and the like.
The compound (37) can be produced by subjecting the compound
(36) to react with methanesulfonylchloride.
Said reaction is carried out with the presence of a base
usually in a solvent.
The solvent used for the reaction includes, ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
such as chlorobenzene and the like; esters butylacetate,
ethylacetate and the like; organic nitriles such as acetonitrile
and the like; acid amides such as N,N-dimethylformamide and the
like; sulfoxides such as dimethylsulfoxide and the like; and the
mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; alkali metal
hydrides such as sodium hydride and the like; tertiary amines such
as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar ratio applied to methanesulfonyl chloride is usually
from 1 to 3 moles per 1 mole of the compound (36) and that of the
base is usually from 1 to 10 moles.
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from -20
to 100 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as concentration, the
concentrated residue being added with an organic solvent to be
filtrated, subsequently concentrating the filtrate, to isolate
the compound (37).
The compound (39) can be produced by subjecting the compound
(37) to react with the compound (38).
Said reaction is usually carried out in a solvent with the
presence of a base.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
such as chlorobenzene and the like; esters butylacetate,
ethylacetate and the like; organic nitriles such as acetonitrile
and the like; acid amides such as N,N-dimethylformamide and the
like; sulfoxides such as dimethylsulfoxide and the like; and the
mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; alkali metal
hydrides such as sodium hydride and the like; tertiary amines such
as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar ratio applied to the compound (38) is usually from
1 to excessive amount per 1 mole of the compound (37) and that
of the base is usually from the catalytic amount to 5 moles.
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from 50
to 150 °C.
After completion of the reaction, the compound (39) can be
isolated by being subjected to post treatment procedure exemplified
below.
The compound (50) can be produced by subjecting the compound
(39) to hydrolysis in the presence of a base (such as sodium hydroxide,
potassium hydroxide and the like).
The reaction is usually carried out in a solvent such as
mixture of water and an alcohol (, for example, methanol, ethanol
and the like) and the like.
The molar ratio applied to the base is usually from 1 to
20 moles per 1 mole of the compound (39).
The reaction time is usually in the range of from 0.5 to
24 hours, and the reaction temperature is in the range of from
0 to 120 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure, such as, after being made
acidity with an acid such as hydrochloric acid and the like,
extracting with organic solvent, subsequently drying and
concentrating the organic layer, to isolate the compound (50).
The isolated compound (50) can be purified by a technique such
as chromatography, recrystallization and the like.
The compound (100) in the compound (50) wherein R1, R4 and
R5 are hydrogen atoms and R15 is a 2-propynyl group, is one of the
important production intermediates in the present invention.
(, wherein, in the formula, R2 and R3 independently represent a
hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl
group, a C2-C6 alkenyl group, a C2-C6 haloalkenyl group, a C2-C6
alkynyl group, a C2-C6 haloalkynyl group, a C1-C6 alkoxy group,
a C1-C6 haloalkoxy group, a C3-C6 alkenyloxy group, a C3-C6
haloalkenyloxy group, a C3-C6 alkynyloxy group, a C3-C6
haloalkynyloxy group, a C1-C6 alkylthio group, a C1-C6
haloalkylthio group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy
group or a cyano group; or R2 and R3 are combined at the terminals
thereof to represent a trimethylene, a tetramethylene or -CH=CH
―CH=CH―.)
The compound (43) can be produced according to, for example,
(Intermediate Compound Production Method 5).
[, wherein, in the formula, L11 represents a chlorine atom or a
bromine atom; L12 and L13 are same or different each other and represent
an alkoxy group such as a methoxy group and the like; R1, R2, R3,
R4, R5, R6, R7, R8 R9, R10, R11 and W1―W2=W3―W4 represent same meaning
defined in [Invention 1]; and X represents same meaning described
above.]
The compound (48) can be produced by subjecting the compound
(46) to react with the compound (47).
Said reaction is usually carried out in a solvent with the
presence of a base.
The solvent used for the reaction includes, ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
such as chlorobenzene and the like; esters butylacetate,
ethylacetate and the like; organic nitriles such as acetonitrile
and the like; acid amides such as N,N-dimethylformamide and the
like; sulfoxides such as dimethylsulfoxide and the like; and the
mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; alkali metal
hydrides such as sodium hydride and the like; tertiary amines such
as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar ratio applied to the compound (47) is usually from
0.5 to 2 moles per 1 mole of the compound (46) and that to the
base is from 1 to 10 moles.
The reaction time is usually in the range of from 0.1 to
24 hours, and the reaction temperature is in the range of from
0 to 150 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (48). The isolated compound (48)
can be purified by a technique such as chromatography,
recrystallization and the like.
The compound (49) can be produced by subjecting the compound
(48) to react with the compound (48-1) or the compound (48-2).
Said reaction is usually carried out in a solvent.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
t-butylmethylether and the like, aliphatic hydrocarbons such as
hexane, heptane and the like, aromatic hydrocarbons such as toluene
and the like, halogenated hydrocarbons such as chlorobenzene and
the like, organic bases such as pyridine, triethylamine,
N,N-dimethylaniline and the like, N,N-dimethylformamide or the
mixture thereof.
The molar ratio applied to the compound (48-1) or the compound
(48-2) is usually from 1 to 10 moles per 1 mole of the compound
(48).
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from 50
to 150 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (49). The isolated compound (49)
can be purified by a technique such as chromatography,
recrystallization and the like.
The compound (43) can be produced by subjecting the compound
(49) to react with water in the presence of an acid.
Said reaction may be carried out in water as the solvent
or in the mixture of water and other organic solvents.
The other organic solvents include ethers such as 1, 4-dioxane,
tetrahydrofuran, ethyleneglycoldimethylether,
t-butylmethylether and the like, aliphatic hydrocarbons such as
hexane, heptane and the like, aromatic hydrocarbons such as toluene
and the like, halogenated hydrocarbons such as chlorobenzene and
the like, organic nitriles such as acetonitrile and the like;
N,N-dimethylformamide, dimethylsulfoxide and the mixture thereof.
The acid used for the reaction includes hydrochloric acid,
sulfuric acid, p-toluenesulfonic acid and the like.
The molar ratio applied to the acid is usually from 0.1 to
100 moles per 1 mole of the compound (49).
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from 20
to 100 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, subsequently drying and concentrating the organic
layer, to isolate the compound (43). The isolated compound (43)
can be purified by a technique such as chromatography,
recrystallization and the like.
The compound (26) can be produced according to (Intermediate
Compound Production Method 6).
(, wherein, in the formula, L4 represents a chlorine atom or a bromine
atom, L5 represents a chlorine atom, a bromine atom or an iodine
atom, and R1, R2, R3, R4, R5 and W1―W2=W3―W4 represent same meaning
defined in [Invention 1].)
The compound (25) can be produced by subjecting the compound
(23) to react with the compound (24).
Said reaction is usually carried out in a solvent with the
presence of a base.
The solvent used for the reaction includes ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; halogenated hydrocarbons
such as chlorobenzene and the like; esters such as ethylacetate,
butylacetate and the like; organic nitriles such as acetonitrile,
butyronitrile and the like; acid amides such as
N,N-dimethylformamide and the like; sulfoxides such as
dimethylsulfoxide and the like; and the mixture thereof.
The base used for the reaction includes carbonates such as
sodium carbonate, potassium carbonate and the like; tertiary amines
such as triethylamine, diisopropylethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene,
1,5-diazabicyclo[4.3.0]non-5-ene and the like; and
nitrogen-contained aromatic compounds such as pyridine,
4-dimethylaminopyridine and the like.
The molar ratio applied to the compound (23) is usually from
1 to 3 moles per 1 mole of the compound (23) and that of the base
is usually from 1 to 10 moles.
The reaction time is usually in the range of from 1 to 24
hours, and the reaction temperature is in the range of from -20
to 100 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent, if necessary, the organic layer being washed by
acidic water, basic water and the like, subsequently drying and
concentrating the organic layer, to isolate the compound (25).
The isolated compound (25) can be purified by a technique such
as chromatography, recrystallization and the like.
The compound (26) can be produced by subjecting the compound
(25) to react with a reducing agent.
Said reaction is carried out in a solvent.
The reducing agent used for the reaction includes sodium
borohydride and potassium borohydride.
The solvent used for the reaction includes alcohols such
as methanol, ethanol, 2-propanol and the like; ethers such as
1,4-dioxane, tetrahydrofuran, ethyleneglycoldimethylether,
tert-butylmethylether and the like; aliphatic hydrocarbons such
as hexane, heptane, octane and the like; aromatic hydrocarbons
such as toluene, xylene and the like; water and the mixture thereof.
The molar ratio applied to the reducing agent is usually
from 0.25 to 3 moles per 1 mole of the compound (25).
The reaction time is usually in the range of from the instant
to 24 hours, and the reaction temperature is in the range of from
-20 to 100 °C.
After completion of the reaction, the reaction mixture is
subjected to post treatment procedure such as extracting with
organic solvent after being added to an acidic water such as aqueous
saturated ammonium chloride and the like, the organic layer obtained
being washed by basic water, subsequently drying and concentrating
the organic layer, to isolate the compound (26). The isolated
compound (26) can be purified by a technique such as chromatography,
recrystallization and the like.
The specific examples of the compound of the present invention
are illustrated below:
R2a | R3a | A1 | A2 | R9a | R10a | Xa |
H | H | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | F | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | Cl | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | Br | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | CH3 | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | CH2CH3 | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | CH2CH2CH3 | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | CH(CH3)2 | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | CH=CH2 | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | C≡CH | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | C≡CCH3 | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | OCH3 | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | OCH2CH3 | H | OCH2C≡CH | OCH3 | OCH3 | O |
-CH2CH2CH2- | H | OCH2C≡CH | OCH3 | OCH3 | O | |
-CH2CH2CH2CH2- | H | OCH2C≡CH | OCH3 | OCH3 | O | |
-CH=CH-CH=CH- | H | OCH2C≡CH | OCH3 | OCH3 | O | |
CH3 | H | H | OCH2C≡CH | OCH3 | OCH3 | O |
Cl | H | H | OCH2C≡CH | OCH3 | OCH3 | O |
CH3 | CH3 | H | OCH2C≡CH | OCH3 | OCH3 | O |
Cl | Cl | H | OCH2C≡CH | OCH3 | OCH3 | O |
H | H | H | OCH2C≡CH | OCH3 | OCH3 | S |
H | Cl | H | OCH2C≡CH | OCH3 | OCH3 | S |
H | Br | H | OCH2C≡CH | OCH3 | OCH3 | S |
H | CH3 | H | OCH2C≡CH | OCH3 | OCH3 | S |
-CH2CH2CH2CH2- | H | OCH2C≡CH | OCH3 | OCH3 | S | |
H | H | H | OH | OCH3 | OCH3 | O |
H | F | H | OH | OCH3 | OCH3 | O |
H | Cl | H | OH | OCH3 | OCH3 | O |
H | Br | H | OH | OCH3 | OCH3 | O |
H | CH3 | H | OH | OCH3 | OCH3 | O |
H | CH2CH3 | H | OH | OCH3 | OCH3 | O |
H | CH2CH2CH3 | H | OH | OCH3 | OCH3 | O |
H | CH(CH3)2 | H | OH | OCH3 | OCH3 | O |
H | CH=CH2 | H | OH | OCH3 | OCH3 | O |
H | C≡CH | H | OH | OCH3 | OCH3 | O |
H | C≡CCH3 | H | OH | OCH3 | OCH3 | O |
H | OCH3 | H | OH | OCH3 | OCH3 | O |
H | OCH2CH3 | H | OH | OCH3 | OCH3 | O |
-CH2CH2CH2- | H | OH | OCH3 | OCH3 | O | |
-CH2CH2CH2CH2- | H | OH | OCH3 | OCH3 | O | |
-CH=CH-CH=CH- | H | OH | OCH3 | OCH3 | O | |
CH3 | H | H | OH | OCH3 | OCH3 | O |
Cl | H | H | OH | OCH3 | OCH3 | O |
CH3 | CH3 | H | OH | OCH3 | OCH3 | O |
Cl | Cl | H | OH | OCH3 | OCH3 | O |
H | H | H | OH | OCH3 | OCH3 | S |
H | Cl | H | OH | OCH3 | OCH3 | S |
H | Br | H | OH | OCH3 | OCH3 | S |
H | CH3 | H | OH | OCH3 | OCH3 | S |
-CH2CH2CH2CH2- | H | OH | OCH3 | OCH3 | S | |
H | H | H | OCH3 | OCH3 | OCH3 | O |
H | F | H | OCH3 | OCH3 | OCH3 | O |
H | Cl | H | OCH3 | OCH3 | OCH3 | O |
H | Br | H | OCH3 | OCH3 | OCH3 | O |
H | CH3 | H | OCH3 | OCH3 | OCH3 | O |
H | CH2CH3 | H | OCH3 | OCH3 | OCH3 | O |
H | CH2CH2CH3 | H | OCH3 | OCH3 | OCH3 | O |
H | CH(CH3)2 | H | OCH3 | OCH3 | OCH3 | O |
H | CH=CH2 | H | OCH3 | OCH3 | OCH3 | O |
H | C≡CH | H | OCH3 | OCH3 | OCH3 | O |
H | C≡CCH3 | H | OCH3 | OCH3 | OCH3 | O |
H | OCH3 | H | OCH3 | OCH3 | OCH3 | O |
H | OCH2CH3 | H | OCH3 | OCH3 | OCH3 | O |
-CH2CH2CH2- | H | OCH3 | OCH3 | OCH3 | O | |
-CH2CH2CH2CH2- | H | OCH3 | OCH3 | OCH3 | O | |
-CH=CH-CH=CH- | H | OCH3 | OCH3 | OCH3 | O | |
CH3 | H | H | OCH3 | OCH3 | OCH3 | O |
Cl | H | H | OCH3 | OCH3 | OCH3 | O |
CH3 | CH3 | H | OCH3 | OCH3 | OCH3 | O |
Cl | Cl | H | OCH3 | OCH3 | OCH3 | O |
H | H | H | OCH3 | OCH3 | OCH3 | S |
H | Cl | H | OCH3 | OCH3 | OCH3 | S |
H | Br | H | OCH3 | OCH3 | OCH3 | S |
H | CH3 | H | OCH3 | OCH3 | OCH3 | S |
-CH2CH2CH2CH2- | H | OCH3 | OCH3 | OCH3 | S | |
H | H | =NOCH3 | OCH3 | OCH3 | O | |
H | F | =NOCH3 | OCH3 | OCH3 | O | |
H | Cl | =NOCH3 | OCH3 | OCH3 | O | |
H | Br | =NOCH3 | OCH3 | OCH3 | O | |
H | CH3 | =NOCH3 | OCH3 | OCH3 | O | |
H | CH2CH3 | =NOCH3 | OCH3 | OCH3 | O | |
H | CH2CH2CH3 | =NOCH3 | OCH3 | OCH3 | O | |
H | CH(CH3)2 | =NOCH3 | OCH3 | OCH3 | O | |
H | CH=CH2 | =NOCH3 | OCH3 | OCH3 | O | |
H | C≡CH | =NOCH3 | OCH3 | OCH3 | O | |
H | C≡CCH3 | =NOCH3 | OCH3 | OCH3 | O | |
H | OCH3 | =NOCH3 | OCH3 | OCH3 | O | |
H | OCH2CH3 | =NOCH3 | OCH3 | OCH3 | O | |
-CH2CH2CH2- | =NOCH3 | OCH3 | OCH3 | O | ||
-CH2CH2CH2CH2- | =NOCH3 | OCH3 | OCH3 | O | ||
-CH=CH-CH=CH- | =NOCH3 | OCH3 | OCH3 | O | ||
CH3 | H | =NOCH3 | OCH3 | OCH3 | O | |
Cl | H | =NOCH3 | OCH3 | OCH3 | O | |
CH3 | CH3 | =NOCH3 | OCH3 | OCH3 | O | |
Cl | Cl | =NOCH3 | OCH3 | OCH3 | O | |
H | H | =NOCH3 | OCH3 | OCH3 | S | |
H | Cl | =NOCH3 | OCH3 | OCH3 | S | |
H | Br | =NOCH3 | OCH3 | OCH3 | S | |
H | CH3 | =NOCH3 | OCH3 | OCH3 | S | |
-CH2CH2CH2CH2- | =NOCH3 | OCH3 | OCH3 | S | ||
H | H | H | OCH2CH3 | OCH3 | OCH3 | O |
H | F | H | OCH2CH3 | OCH3 | OCH3 | O |
H | Cl | H | OCH2CH3 | OCH3 | OCH3 | O |
H | Br | H | OCH2CH3 | OCH3 | OCH3 | O |
H | CH3 | H | OCH2CH3 | OCH3 | OCH3 | O |
-CH2CH2CH2CH2- | H | OCH2CH3 | OCH3 | OCH3 | O | |
H | H | H | OCH2CF3 | OCH3 | OCH3 | O |
H | F | H | OCH2CF3 | OCH3 | OCH3 | O |
H | Cl | H | OCH2CF3 | OCH3 | OCH3 | O |
H | Br | H | OCH2CF3 | OCH3 | OCH3 | O |
H | CH3 | H | OCH2CF3 | OCH3 | OCH3 | O |
-CH2CH2CH2CH2- | H | OCH2CF3 | OCH3 | OCH3 | O | |
H | H | H | OCH2CH2CH3 | OCH3 | OCH3 | O |
H | F | H | OCH2CH2CH3 | OCH3 | OCH3 | O |
H | Cl | H | OCH2CH2CH3 | OCH3 | OCH3 | O |
H | Br | H | OCH2CH2CH3 | OCH3 | OCH3 | O |
H | CH3 | H | OCH2CH2CH3 | OCH3 | OCH3 | O |
-CH2CH2CH2CH2- | H | OCH2CH2CH3 | OCH3 | OCH3 | O | |
H | H | H | OCH2CH=CH2 | OCH3 | OCH3 | O |
H | F | H | OCH2CH=CH2 | OCH3 | OCH3 | O |
H | Cl | H | OCH2CH=CH2 | OCH3 | OCH3 | O |
H | Br | H | OCH2CH=CH2 | OCH3 | OCH3 | O |
H | CH3 | H | OCH2CH=CH2 | OCH3 | OCH3 | O |
-CH2CH2CH2CH2- | H | OCH2CH=CH2 | OCH3 | OCH3 | O | |
CH3 | H | H | OCH2CH3 | OCH3 | OCH3 | O |
H | H | =NOCH2CH3 | OCH3 | OCH3 | O | |
H | F | =NOCH2CH3 | OCH3 | OCH3 | O | |
H | Cl | =NOCH2CH3 | OCH3 | OCH3 | O | |
H | Br | =NOCH2CH3 | OCH3 | OCH3 | O | |
H | CH3 | =NOCH2CH3 | OCH3 | OCH3 | O | |
H | H | =NOCH2F | OCH3 | OCH3 | O | |
H | F | =NOCH2F | OCH3 | OCH3 | O | |
H | Cl | =NOCH2F | OCH3 | OCH3 | O | |
H | Br | =NOCH2F | OCH3 | OCH3 | O | |
H | CH3 | =NOCH2F | OCH3 | OCH3 | O | |
H | H | =CCl2 | OCH3 | OCH3 | O | |
H | F | =CCl2 | OCH3 | OCH3 | O | |
H | Cl | =CCl2 | OCH3 | OCH3 | O | |
H | Br | =CCl2 | OCH3 | OCH3 | O | |
H | CH3 | =CCl2 | OCH3 | OCH3 | O | |
H | H | =CHOCH2F | OCH3 | OCH3 | O | |
H | F | =CHOCH2F | OCH3 | OCH3 | O | |
H | Cl | =CHOCH2F | OCH3 | OCH3 | O | |
H | Br | =CHOCH2F | OCH3 | OCH3 | O | |
H | CH3 | =CHOCH2F | OCH3 | OCH3 | O | |
-CH2CH2CH2CH2- | =NOCH2CH3 | OCH3 | OCH3 | O | ||
-CH2CH2CH2CH2- | =NOCH2F | OCH3 | OCH3 | O | ||
-CH2CH2CH2CH2- | =CCl2 | OCH3 | OCH3 | O | ||
-CH2CH2CH2CH2- | =CHOCH2F | OCH3 | OCH3 | O | ||
-CH2CH2CH2CH2- | =CCl2 | OCH3 | OCH3 | S | ||
H | H | H | OCO2CH3 | OCH3 | OCH3 | O |
H | F | H | OCO2CH3 | OCH3 | OCH3 | O |
H | Cl | H | OCO2CH3 | OCH3 | OCH3 | O |
H | Br | H | OCO2CH3 | OCH3 | OCH3 | O |
H | CH3 | H | OCO2CH3 | OCH3 | OCH3 | O |
-CH2CH2CH2CH2- | H | OCO2CH3 | OCH3 | OCH3 | O | |
H | H | H | OCO2CH2CH3 | OCH3 | OCH3 | O |
H | F | H | OCO2CH2CH3 | OCH3 | OCH3 | O |
H | Cl | H | OCO2CH2CH3 | OCH3 | OCH3 | O |
H | Br | H | OCO2CH2CH3 | OCH3 | OCH3 | O |
H | CH3 | H | OCO2CH2CH3 | OCH3 | OCH3 | O |
-CH2CH2CH2CH2- | H | OCO2CH2CH3 | OCH3 | OCH3 | O | |
H | H | H | OCH2C≡CCH3 | OCH3 | OCH3 | O |
H | F | H | OCH2C≡CCH3 | OCH3 | OCH3 | O |
H | Cl | H | OCH2C≡CCH3 | OCH3 | OCH3 | O |
H | Br | H | OCH2C≡CCH3 | OCH3 | OCH3 | O |
H | CH3 | H | OCH2C≡CCH3 | OCH3 | OCH3 | O |
-CH2CH2CH2CH2- | H | OCH(CH3)C≡CCH3 | OCH3 | OCH3 | O | |
H | H | H | OCH (CH3)C ≡CCH3 | OCH3 | OCH3 | O |
H | F | H | OCH (CH3)C≡CCH3 | OCH3 | OCH3 | O |
H | Cl | H | OCH(CH3)C ≡CCH3 | OCH3 | OCH3 | O |
H | Br | H | OCH (CH3)C≡CCH3 | OCH3 | OCH3 | O |
H | CH3 | H | OCH(CH3)C ≡CCH3 | OCH3 | OCH3 | O |
-CH2CH2CH2CH2- | H | OCH (CH3)C≡CCH3 | OCH3 | OCH3 | O | |
-CH2CH2CH2- | H | OCH2C≡CCH3 | OCH3 | OCH3 | O | |
H | H | H | OCH2C≡CH | OCH2CH3 | OCH2CH3 | O |
H | F | H | OCH2C≡CH | OCH2CH3 | OCH2CH3 | O |
H | Cl | H | OCH2C≡CH | OCH2CH3 | OCH2CH3 | O |
H | Br | H | OCH2C≡CH | OCH2CH3 | OCH2CH3 | O |
H | CH3 | H | OCH2C≡CH | OCH2CH3 | OCH2CH3 | O |
-CH2CH2CH2CH2- | H | OCH2C≡CH | OCH2CH3 | OCH2CH3 | O | |
H | H | H | OCH2C≡CH | OCH2CH3 | OCH3 | O |
H | F | H | OCH2C≡CH | OCH2CH3 | OCH3 | O |
H | Cl | H | OCH2C≡CH | OCH2CH3 | OCH3 | O |
H | Br | H | OCH2C≡CH | OCH2CH3 | OCH3 | O |
H | CH3 | H | OCH2C≡CH | OCH2CH3 | OCH3 | O |
-CH2CH2CH2CH2- | H | OCH2C≡CH | OCH2CH3 | OCH3 | O | |
H | H | H | OCH2C≡CH | OCH2C≡CH | OCH3 | O |
H | F | H | OCH2C≡CH | OCH2C≡CH | OCH3 | O |
H | Cl | H | OCH2C≡CH | OCH2C≡CH | OCH3 | O |
H | Br | H | OCH2C≡CH | OCH2C≡CH | OCH3 | O |
H | CH3 | H | OCH2C≡CH | OCH2C≡CH | OCH3 | O |
-CH2CH2CH2CH2- | H | OCH2C≡CH | OCH2C≡CH | OCH3 | O | |
H | H | H | OCH2C≡CH | OCH3 | OCH2CH3 | O |
H | F | H | OCH2C≡CH | OCH3 | OCH2CH3 | O |
H | Cl | H | OCH2C≡CH | OCH3 | OCH2CH3 | O |
H | Br | H | OCH2C≡CH | OCH3 | OCH2CH3 | O |
H | CH3 | H | OCH2C≡CH | OCH3 | OCH2CH3 | O |
-CH2CH2CH2CH2- | H | OCH2CH=CH2 | OCH3 | OCH2CH3 | O | |
H | CH3 | H | OCH2C≡CH | OCH2CH3 | OCH2CH3 | S |
H | H | H | OCH2C≡CH | OCH3 | OCH2C≡CH | O |
H | F | H | OCH2C≡CH | OCH3 | OCH2C≡CH | O |
H | Cl | H | OCH2C≡CH | OCH3 | OCH2C≡CH | O |
H | Br | H | OCH2C≡CH | OCH3 | OCH2C≡CH | O |
H | CH3 | H | OCH2C≡CH | OCH3 | OCH2C≡CH | O |
-CH2CH2CH2CH2- | H | OCH2C≡CH | OCH3 | OCH2C≡CH | O |
Following is the illustration exemplifying the compound (100)
which is the important intermediate in the present invention.
A compound represented by the formula (V)
, wherein, in the formula(V), R2a, R3a, A1, and A2 represent
the combination of substituted groups exhibited in (Table 2).
R2a | R3a | A1 | A2 |
H | H | H | OCH2C≡CH |
H | F | H | OCH2C≡CH |
H | Cl | H | OCH2C≡CH |
H | Br | H | OCH2C≡CH |
H | CH3 | H | OCH2C≡CH |
H | CH2CH3 | H | OCH2C≡CH |
H | CH2CH2CH3 | H | OCH2C≡CH |
H | CH(CH3)2 | H | OCH2C≡CH |
H | CH=CH2 | H | OCH2C≡CH |
H | C≡CH | H | OCH2C≡CH |
H | C≡CCH3 | H | OCH2C≡CH |
H | OCH3 | H | OCH2C≡CH |
H | OC2H5 | H | OCH2C≡CH |
-CH2CH2CH2- | H | OCH2C≡CH | |
-CH2CH2CH2CH2- | H | OCH2C≡CH | |
-CH=CH-CH=CH- | H | OCH2C≡CH | |
CH3 | H | H | OCH2C≡CH |
Cl | H | H | OCH2C≡CH |
CH3 | CH3 | H | OCH2C≡CH |
Cl | Cl | H | OCH2C≡CH |
Plant diseases against which the compound of the present
invention has controlling activity include, for example, a disease
due to Phycomycetes, specifically following diseases are
illustrated:
The fungicidal composition of the present invention comprises
the compound of the present invention and a carrier. The carrier
is inert to the compound of the present invention and appropriately
chosen depending on types applying the fungicidal composition of
the present invention and the like. The fungicidal composition
of the present invention may further comprise adjuvant for
formulation such as surfactant and the like depending on the
necessity. The fungicidal composition of the present invention
includes formulation forms such as emulsifiable concentrate,
wettable powder, dry flowable, flowable, dust, granule and the
like. The fungicidal composition of the present invention usually
contains 0.1 to 90 % by weight of the compound of the present
invention.
Solid carriers used for the fungicidal composition of the
present invention include, for example, fine powders or granules
of minerals such as kaolin clay, attapulgite clay, bentonite,
montmorillonite, terra alba, pyrophyllite, talc, diatomaceous
earth, calcite and the like; natural organic substances such as
corncob powder, walnut shell powder and the like; synthetic organic
substances such as urea and the like; salts such as calcium carbonate,
ammonium sulfate and the like; synthetic inorganic substances such
as synthetic hydrous silicon oxide and the like. Liquid carriers
include, for example, aromatic hydrocarbons such as xylene,
alkylbenzene, methylnaphthalene and the like; alcohols such as
2-propanol, ethylene glycol, propylene glycol, cellosolve and the
like; ketones such as acetone, cyclohexanone, isophorone and the
like; vegetable oils such as soybean oil, cottonseed oil and the
like; petroleum aliphatic hydrocarbons, esters, dimethylsulfoxide,
acetonitrile and water.
Surfactants include, for example, anionic surfactants such
as alkylsulfuric acid ester salt, alkylarylsulfonic acid salt,
dialkylsulfosuccinic acid salt,
polyoxyethylenealkylaryletherphosphoric acid ester salt, lignin
sulfonic acid salt, polycondensed
naphthalenesulfonateformaldehyde and the like; and nonionic
surfactants such as polyoxyethylenealkylarylether,
polyoxyethylenealkylpolyoxypropylene block copolymer, sorbitan
fatty acid ester and the like.
Another adjuvant for formulation includes, for example,
water-soluble polymers such as polyvinylalcohol,
polyvinylpyrrolidone and the like; Arabian gum; alginic acid and
its salt thereof; polysaccharides such as
CMC(carboxymethylcellulose), xanthan gum and the like; inorganic
substances such as alminum magnesium silicate, alumina sol and
the like; and antiseptics, colorants, PAP(isopropyl acidic
phosphate), stabilizers such as BHT and the like.
By applying the fungicidal composition of the present
invention to treatment for plants, said plants can be protected
from plant diseases; and by applying the fungicidal composition
of the present invention to treatment for soils, said plants grown
on said soils can be protected from plant diseases.
When the fungicidal composition of the present invention
is applied to foliage treatment for plants or soil treatment, the
application amount thereof, which may be varied with a kind of
control-object plants, a kind and an infestation level of
control-object diseases, formulation types, application timings,
weather conditions and the like, is usually 1 to 5000 g of the
compound of the present invention per 10000 m2, preferably 5 to
1000 g.
Emulsifiable concentrate, wettable powder, flowable and the
like are usually sprayed after diluted with water. In this case,
the concentration of the compound of the present invention is usually
in the range of from 0.0001 to 3 % by weight, preferably from 0.0005
to 1 % by weight. Dust, granule and the like are usually directly
used without dilution.
The fungicidal composition of the present invention can be
also applied in treatment methods such as seed disinfection and
the like. The methods include, for example, a method to soak seeds
of a plant in the liquid fungicidal composition of the present
invention which prepared in 1 to 1000 ppm in terms of concentration
of the compound of the present invention, a method to spray or
coat seeds of a plant with the liquid fungicidal composition of
the present invention which prepared in 1 to 1000 ppm in terms
of concentration of the compound of the present invention, and
a method to coat seeds of a plant with the powder of the composition
controlling plant diseases of the present invention.
The method for controlling plant diseases of the present
invention is performed by applying effective amount of the compound
of the present invention to a plant or a soil growing the plant
in which infection is predictable and/or to a plant or a soil growing
the plant in which infection is confirmed.
The fungicidal composition of the present invention is
usually used as an agent controlling plant diseases for agriculture
or gardening, that is, as an agent controlling plant diseases to
control plant diseases on plowed fields, paddy fields, orchards,
tea fields, pastures, lawn and the like.
The fungicidal composition of the present invention may be
used together with other plant disease controlling compositions,
pesticides, acaricides, nematicides, herbicides, plant growth
regulators and/or fertilizers.
Examples of the active ingredient of such other plant diseases
controlling composition include:
The present invention is further illustrated in detail with
production examples, formulation examples, test examples and other
manner, but should not be construed to be limited thereto.
At first, the production examples are illustrated as follows.
2g of N-(3-bromopyridine-2-yl)-2,2-dimethylpropionamide,
1.4 g of 3,4-dimethoxyphenylboronic acid, 5 g of tripotassium
phosphate hydrate, 190 mg of
{1,1'-bis(diphenylphosphino)ferrocene}dichloropalladium(II)
methylenechloride complex and 50 ml of ethyleneglycoldimethylether
were mixed, followed by stirring under a nitrogen atmosphere at
80 °C for 2 hours. Then, the reaction mixture was added to water
to be extracted with ethyl acetate. The organic layer was
concentrated under reduced pressure and then the concentrated
residue obtained was subjected to a silica gel column chromatography
(eluent; ethylacetate) to obtain 2.1 g of
N-(3-(3,4-dimethoxyphenyl)pyridine-2-yl)-2,2-dimethylpropionamide.
1H-NMR(CDCl3,TMS)δ(ppm): 1.15(9H,s), 3.89(3H,s), 3.94(3H,s), 6.87-6.98(3H,m), 7.17(1H,dd,J=4.8Hz,7.6Hz), 7.61(1H,dd,J=2.0Hz,7.6Hz), 7.69(1H,s), 8.47(1H,dd,J=2.0Hz,4.8Hz)
1H-NMR(CDCl3,TMS)δ(ppm): 1.15(9H,s), 3.89(3H,s), 3.94(3H,s), 6.87-6.98(3H,m), 7.17(1H,dd,J=4.8Hz,7.6Hz), 7.61(1H,dd,J=2.0Hz,7.6Hz), 7.69(1H,s), 8.47(1H,dd,J=2.0Hz,4.8Hz)
The mixture of 2.1 g of
N-(3-(3,4-dimethoxyphenyl)pyridine-2-yl)-2,2-dimethylpropionamide,
20 ml of methanol and 15 ml of aqueous 3M
potassium hydroxide was heated under reflux for 4 hours. After
being cooled down to room temperature, the reaction mixture was
added with water to be extracted with ethylacetate. The organic
layer was concentrated under reduced pressure and then the
concentrated residue was subjected to a silica gel column
chromatography (eluent; ethylacetate) to obtain 1.2 g of
2-amino-3-(3,4-dimethoxyphenyl)pyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 3.90(3H,s), 3.93(3H,s), 4.62(2H,s), 6.74(1H,dd,J=4.9Hz,7.3Hz), 6.94-7.01(3H,m), 7.36(1H,dd,J=1.7Hz,7.3Hz), 8.06(1H,dd,J=1.7Hz,4.9Hz)
1H-NMR(CDCl3,TMS)δ(ppm): 3.90(3H,s), 3.93(3H,s), 4.62(2H,s), 6.74(1H,dd,J=4.9Hz,7.3Hz), 6.94-7.01(3H,m), 7.36(1H,dd,J=1.7Hz,7.3Hz), 8.06(1H,dd,J=1.7Hz,4.9Hz)
0.5 g of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetyl
chloride (, which was prepared by the method of Referencial
Production Example 1 described hereinafter) was added dropwise
to the mixture of 0.44 g of 2-amino-3-(3,4-dimethoxyphenyl)pyridine,
0.20 g of triethylamine, 0.05 g of 4-dimethylaminopyridine and
15 ml of tetrahydrofuran, followed by stirring at room temperature
for 3 hours. Thereafter, the reaction mixture was added with
ethylacetate and then filtrated to remove insolubles. The filtrate
was concentrated under reduced pressure and then the residue was
subjected to a silica gel column chromatography (eluent;
hexane/ethylacetate =1/1) to obtain 0.31 g of
N-(3-(3,4-dimethoxyphenyl)pyridine-2-yl)-2-(2-propynyloxy)-2-(4-chlorophenyl)
acetamide (, which is referred to as the compound
of the present invention (IV-1) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 2.47 (1H, t,J=2.4Hz), 3.85(3H,s), 3.94(3H,s), 4.01(1H,dd,J=2.4Hz,15.7Hz), 4.18(1H,dd,J=2.4Hz,15.7Hz), 5.05(1H,s), 6.84-6.88(3H,m), 7.18(1H,dd,J=4.8Hz,7.7Hz), 7.28-7.33(4H,m), 7.63(1H,dd,J=1.7Hz,7.7Hz), 8.47(1H,dd,J=1.7Hz,4.8Hz), 8.79(1H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 2.47 (1H, t,J=2.4Hz), 3.85(3H,s), 3.94(3H,s), 4.01(1H,dd,J=2.4Hz,15.7Hz), 4.18(1H,dd,J=2.4Hz,15.7Hz), 5.05(1H,s), 6.84-6.88(3H,m), 7.18(1H,dd,J=4.8Hz,7.7Hz), 7.28-7.33(4H,m), 7.63(1H,dd,J=1.7Hz,7.7Hz), 8.47(1H,dd,J=1.7Hz,4.8Hz), 8.79(1H,s)
12 g of 4-chloro-3-nitropyridine, 11 g of
3,4-dimethoxyphenylboronic acid, 39 g of tripotassium phosphate
hydrate, 988 mg of
{1,1'-bis(diphenylphosphino)ferrocene}dichloropalladium(II)
methylenechloride complex and 100 ml of
ethyleneglycoldimethylether were mixed, followed by stirring under
a nitrogen atmosphere at 80 °C for 2 hours. Then, the reaction
mixture was added with water to be extracted with ethylacetate.
The organic layer was dried by anhydrous magnesium sulfate and
then concentrated under reduced pressure, followed by the residue
being subjected to a silica gel column chromatography (eluent;
hexane/ethylacetate =1/1) to obtain 13 g of
4-(3,4-dimethoxyphenyl)-3-nitropyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 3.89(3H,s), 3.94(3H,s), 6.83-6.96(3H,m), 7.42(1H,d,J=4.8Hz), 8.76(1H,d,J=4.8Hz), 9.00(1H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 3.89(3H,s), 3.94(3H,s), 6.83-6.96(3H,m), 7.42(1H,d,J=4.8Hz), 8.76(1H,d,J=4.8Hz), 9.00(1H,s)
5.0 g of 4-(3,4-dimethoxyphenyl) -3-nitropyridine was added
to the mixture of 25 ml of acetic acid, 25 ml of water and 4.3
g of iron powder at 70 °C, followed by stirring for 2 hours. Then,
the reaction mixture was added with aqueous sodium bicarbonate
to be extracted with ethylacetate. The organic layer was
concentrated under reduced pressure and then the residue was
subjected to a silica gel column chromatography (eluent;
hexane/ethylacetate =1/1) to obtain 3.2 g of
3-amino-4-(3,4-dimethoxyphenyl)pyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 3.83 (2H,s), 3.91(3H,s), 3.93(3H,s), 6.95-7.05(4H,m), 8.05(1H,d,J=4.8Hz), 8.14(1H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 3.83 (2H,s), 3.91(3H,s), 3.93(3H,s), 6.95-7.05(4H,m), 8.05(1H,d,J=4.8Hz), 8.14(1H,s)
0.4 g of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetyl
chloride was added dropwise to the mixture of 0.40 g of
3-amino-4-(3, 4-dimethoxyphenyl) pyridine, 0.21 g of triethylamine
and 10 ml of tetrahydrofuran, followed by stirring at room
temperature for 2 hours. Then, the reaction mixture was added with
ethyl acetate and then filtrated to remove insolubles. The filtrate
was concentrated under reduced pressure and then the residue was
subjected to a silica gel column chromatography (eluent;
hexane/ethylacetate =1/1) to obtain 0.50 g of
N-(4-(3,4-dimethoxyphenyl)pyridine-3-yl)-2-(2-propynyloxy)-2-(4-chlorophenyl)
acetamide (, which is referred to as the compound
of the present invention (III-1) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 2.49(1H,t,J=2.4Hz), 3.90-3.99(7H,m), 4.16(1H,dd,J=2.4Hz,16.0Hz), 5.08(1H,s), 6.88(1H,d,J=2.0Hz), 6.95(1H,dd,J=2.0Hz,8.3Hz), 7.01(1H,d,J=8.3Hz), 7.21(1H,d,J=4.8Hz), 7.29(2H,d,J=8.3Hz), 7.34(2H,d,J=8.3Hz), 8.42(1H,d,J=4.8Hz), 8.70(1H,s), 9.51(1H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 2.49(1H,t,J=2.4Hz), 3.90-3.99(7H,m), 4.16(1H,dd,J=2.4Hz,16.0Hz), 5.08(1H,s), 6.88(1H,d,J=2.0Hz), 6.95(1H,dd,J=2.0Hz,8.3Hz), 7.01(1H,d,J=8.3Hz), 7.21(1H,d,J=4.8Hz), 7.29(2H,d,J=8.3Hz), 7.34(2H,d,J=8.3Hz), 8.42(1H,d,J=4.8Hz), 8.70(1H,s), 9.51(1H,s)
8.5 g of N-(3-bromopyridine-4-yl)-2,2-dimethylpropionamide,
5.0 g of 3,4-dimethoxyphenylboronic acid, 17.5 g of tripotassium
phosphate hydrate, 670 mg of {1,1'
-bis(diphenylphosphino)ferrocene}dichloropalladium(II)
methylenechloride complex and 100 ml of
ethyleneglycoldimethylether were mixed, followed by stirring under
a nitrogen atmosphere at 80 °C for 2 hours. Then, the reaction
mixture was added with water to be extracted with ethylacetate.
The organic layer was concentrated under reduced pressure, followed
by the residue being subj ected to a silica gel column chromatography
(eluent; ethylacetate) to obtain 8 g of
N-3-(3,4-dimethoxyphenyl)pyridine-4-yl)-2,2-dimethylpropionam
ide.
1H-NMR(CDCl3,TMS)δ(ppm): 1.14(9H,s), 3.91(3H,s), 3.97(3H,s), 6.86(1H,d,J=2.0Hz), 6.93(1H,dd,J=2.0Hz,8.0Hz), 7.03(1H,d,J=8.0Hz), 7.81(1H,s), 8.41(1H,s), 8.42(1H,d,J=5.5Hz), 8.50(1H,d,J=5.5Hz)
4.0 g of N-(3-(3,4-dimethoxyphenyl)pyridine-4-yl)-2,2-dimethylpropiona mide, 20 ml of methanol and 15 ml of aqueous 3M potassium hydroxide were mixed, followed by for 4 hours heating with reflux. Then, the reaction mixture was cooled down to room temperature, and then the reaction mixture was added with water to be extracted by ethylacetate. The organic layer was concentrated under reduced pressure and then the residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 2.3 g of 4-amino-3-(3,4-dimethoxyphenyl)pyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 3.86(2H,s), 3.93(6H,s), 6.95(1H,d,J=8.3Hz), 7.03-7.05(2H,m), 7.22-7.27(2H,m), 8.11(1H,d,J=2.8Hz)
0.4 g of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetyl chloride was added dropwise to the mixture of 0.40 g of 4-amino-3-(3,4-dimethoxyphenyl)pyridine, 0.25 g of triethylamine and 10 ml of tetrahydrofuran, followed by stirring at room temperature for 3 hours. Thereafter, the reaction mixture was added with ethylacetate and then fittrated to remove insolubles. The filtrate was concentrated under reduced pressure and then the residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 0.72 g of N-(3-(3,4-dimethoxyphenyl)pyridine-4-yl)-2-(2-propynyloxy)-2-(4-chlorophenyl)acetamide (, which is referred to as the compound of the present invention (II-1) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 1.14(9H,s), 3.91(3H,s), 3.97(3H,s), 6.86(1H,d,J=2.0Hz), 6.93(1H,dd,J=2.0Hz,8.0Hz), 7.03(1H,d,J=8.0Hz), 7.81(1H,s), 8.41(1H,s), 8.42(1H,d,J=5.5Hz), 8.50(1H,d,J=5.5Hz)
4.0 g of N-(3-(3,4-dimethoxyphenyl)pyridine-4-yl)-2,2-dimethylpropiona mide, 20 ml of methanol and 15 ml of aqueous 3M potassium hydroxide were mixed, followed by for 4 hours heating with reflux. Then, the reaction mixture was cooled down to room temperature, and then the reaction mixture was added with water to be extracted by ethylacetate. The organic layer was concentrated under reduced pressure and then the residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 2.3 g of 4-amino-3-(3,4-dimethoxyphenyl)pyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 3.86(2H,s), 3.93(6H,s), 6.95(1H,d,J=8.3Hz), 7.03-7.05(2H,m), 7.22-7.27(2H,m), 8.11(1H,d,J=2.8Hz)
0.4 g of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetyl chloride was added dropwise to the mixture of 0.40 g of 4-amino-3-(3,4-dimethoxyphenyl)pyridine, 0.25 g of triethylamine and 10 ml of tetrahydrofuran, followed by stirring at room temperature for 3 hours. Thereafter, the reaction mixture was added with ethylacetate and then fittrated to remove insolubles. The filtrate was concentrated under reduced pressure and then the residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 0.72 g of N-(3-(3,4-dimethoxyphenyl)pyridine-4-yl)-2-(2-propynyloxy)-2-(4-chlorophenyl)acetamide (, which is referred to as the compound of the present invention (II-1) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 8.99(1H,s), 8.68-8.71-(1H,m),
8.43(1H,dd,J=4.8Hz,1.6Hz), 7.00-7.37(8H,m), 5.09(1H,s),
3.95-4.20(8H,m), 2.47(1H,t,J=2.4Hz)
To 50 ml of ethyleneglycoldimethylether, 4.76 g of
2-chloro-3-nitropyridine, 6.00 g of 3,4-dimethoxyphenylboronic
acid, 19.1 g of tripotassium phosphate hydrate and 490 mg of {1,1'
-bis(diphenylphosphino)ferrocene}dichloropalladium(II)
methylenechloride complex were added, followed by stirring under
a nitrogen atmosphere at 80°C for 4 hours. Thereafter, the reaction
mixture was cooled down to room temperature followed by filtration,
and then the filtrate was concentrated under reduced pressure.
The residue was subjected to a silica gel column chromatography
to obtain 5.35 g of 2-(3,4-dimethoxyphenyl)-3-nitropyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 8.83(1H,dd,J=1.2Hz,4.6Hz), 8.07(1H,dd,J=1.1Hz,8.3Hz), 7.39(1H,dd,J=4.6Hz,8.3Hz), 7.19(1H,d,J=2.0Hz), 7.12(1H,dd,J=2.0Hz,8.3Hz), 6.93(1H,d,J=8.3Hz), 3.93(6H,s)
2.8 g of 4-(3,4-dimethoxyphenyl)-3-nitropyridine was dissolved to 100 ml of ethanol at room temperature, followed by addition of 150 mg of 5 % platinum-carbon and then stirring under a hydrogen atmosphere for 4 hours. Thereafter, the reaction mixture was filtrated through celite, followed by the filtrate being concentrated under reduced pressure. The residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 2.1 g of 3-amino-2-(3,4-dimethoxyphenyl)pyridine.
Melting point: 213.5 °C
0.85 g of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetyl chloride was added dropwis to the mixture of 0.90 g of 3-amino-2-(3,4-dimethoxyphenyl) pyridine, 0.40 g of triethylamine and 15 ml of tetrahydrofuran, followed by stirring at room temperature for 2 hours. Thereafter, the reaction mixture was added with ethylacetate and then filtrated to remove insolubles. The filtrate was concentrated under reduced pressure and then the residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 1 g of N-(2-(3,4-dimethoxyphenyl)pyridine-3-yl)-2-(2-propynyloxy)-2-(4-chlorophenyl) acetamide (, which is referred to as the compound of the present invention (I-1) hereinafter).
Melting point: 125.2 °C
1H-NMR(CDCl3,TMS)δ(ppm): 8.83(1H,dd,J=1.2Hz,4.6Hz), 8.07(1H,dd,J=1.1Hz,8.3Hz), 7.39(1H,dd,J=4.6Hz,8.3Hz), 7.19(1H,d,J=2.0Hz), 7.12(1H,dd,J=2.0Hz,8.3Hz), 6.93(1H,d,J=8.3Hz), 3.93(6H,s)
2.8 g of 4-(3,4-dimethoxyphenyl)-3-nitropyridine was dissolved to 100 ml of ethanol at room temperature, followed by addition of 150 mg of 5 % platinum-carbon and then stirring under a hydrogen atmosphere for 4 hours. Thereafter, the reaction mixture was filtrated through celite, followed by the filtrate being concentrated under reduced pressure. The residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 2.1 g of 3-amino-2-(3,4-dimethoxyphenyl)pyridine.
Melting point: 213.5 °C
0.85 g of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetyl chloride was added dropwis to the mixture of 0.90 g of 3-amino-2-(3,4-dimethoxyphenyl) pyridine, 0.40 g of triethylamine and 15 ml of tetrahydrofuran, followed by stirring at room temperature for 2 hours. Thereafter, the reaction mixture was added with ethylacetate and then filtrated to remove insolubles. The filtrate was concentrated under reduced pressure and then the residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 1 g of N-(2-(3,4-dimethoxyphenyl)pyridine-3-yl)-2-(2-propynyloxy)-2-(4-chlorophenyl) acetamide (, which is referred to as the compound of the present invention (I-1) hereinafter).
Melting point: 125.2 °C
40.0 g of 4-bromochlorobenzene was dissolved to 140 ml of
tetrahydrofuran under a nitrogen atmosphere and then added with
5.33 g of magnesium, followed by stirring to prepare Grignard reagent.
750 ml of tetrahydrofuran was dissolved with 49.3 g of dimethyl
oxalate, followed by dropping at -70 °C with Grignard reagent
aforementioned for 30 minutes. Thereafter, the reaction mixture
was warmed to room temperature in 2 hours, followed by stirring
at room temperature for 2 hours. Then, the reaction mixture was
added with ice water and aqueous saturated ammonium chloride,
followed by concentration under reduced pressure. The residue was
filtrated, followed by the filtrate being extracted with
ethylacetate. The organic layer was washed by aqueous saturated
sodium chloride and then dried by magnesium sulfate, followed by
concentration under reduced pressure. The residue was subjected
to a silica gel column chromatography to obtain 22.1 g of
4-chlorophenylglyoxylic acid methyl ester.
1H-NMR(CDCl3,TMS)δ(ppm): 7.98-8.01(2H,m), 7.48-7.51(2H,m), 3.98(3H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 7.98-8.01(2H,m), 7.48-7.51(2H,m), 3.98(3H,s)
To 300 ml of ethanol, 12.2 g of 4-chlorophenylglyoxylic acid
methyl ester and 12.6 g of aqueous 20 % sodium hydroxide were added,
followed by stirring at room temperature for 3 hours. Thereafter,
the reaction mixture was acidified by addition of 36 % hydrochloric
acid, followed by extraction in three times with chloroform. The
organic layer was dried by anhydrous magnesium sulfate and then
concentrated under reduced pressure. The residue was washed by
hexane and then dried to obtain 5.2 g of 4-chlorophenylglyoxylic
acid.
1H-NMR(CDCl3,TMS)δ(ppm): 8.36-8.39(1H,m), 8.0(1H,br), 7.51-7.54(2H,m)
1H-NMR(CDCl3,TMS)δ(ppm): 8.36-8.39(1H,m), 8.0(1H,br), 7.51-7.54(2H,m)
To 20 ml of toluene, 1.5 g of 4-chlorophenylglyoxylic acid,
0.95 ml of thionyl chloride and 20 mg of N,N-dimethylformamide
were added, followed by stirring at 80 °C for 1 hour. Thereafter,
the reaction mixture was cooled down to room temperature and then
concentrated under reduced pressure to obtain crude
4-chlorophenylglyoxyl chloride. To the solution prepared by
mixing 1.0 g of 3-amino-2-chloropyridine, 1.7 ml of triethylamine
and 20 ml of tetrahydrofuran; 4-methylphenylglyoxyl chloride
described above was added at the temperature range of from 0 to
5 °C, followed by stirring at room temperature for 2 hours.
Thereafter, the reaction mixture was added with water to be extracted
with ethylacetate. The organic layer obtained was successively
washed by 5 % hydrochloric acid, aqueous saturated sodium
bicarbonate and aqueous saturated sodium chloride and then dried
by magnesium sulfate, followed by concentration under reduced
pressure. The residue was washed by hexane to obtain 1.5 g of
N-(2-chloropyridine-3-yl)-2-oxo-2-(4-chlorophenyl)acetamide.
1H-NMR(CDCl3,TMS)δ(ppm): 9.59(1H,s), 8.84(1H,dd,J=8.0Hz,1.6Hz), 8.42(2H,d,J=8.8Hz), 8.22(dd,1H,J=4.8Hz,1.6Hz), 7.52(2H,d,J=8.8Hz), 7.35(dd,1H,J=8.4Hz,4.7Hz)
1H-NMR(CDCl3,TMS)δ(ppm): 9.59(1H,s), 8.84(1H,dd,J=8.0Hz,1.6Hz), 8.42(2H,d,J=8.8Hz), 8.22(dd,1H,J=4.8Hz,1.6Hz), 7.52(2H,d,J=8.8Hz), 7.35(dd,1H,J=8.4Hz,4.7Hz)
To 10 ml of ethanol, 1.0 g of
N-(2-chloropyridine-3-yl)-2-oxo-2-(4-chlorophenyl)acetamide
was dissolved and was added with 38 mg of sodium borohydride at
0 °C, followed by further stirring at room temperature for 1 hour.
Thereafter, the reaction mixture was added with aqueous saturated
ammonium chloride to be extracted with ethylacetate. The organic
layer was successively washed by aqueous saturated sodium
bicarbonate and aqueous saturated sodium chloride and then dried
by magnesium sulfate, followed by concentration under reduced
pressure to obtain 1.0 g of
N-(2-chloropyridine-3-yl)-2-hydroxy-2-(4-chlorophenyl)acetami
de.
1H-NMR(CDCl3,TMS)δ(ppm): 9.00(1H,s), 8.71(1H,dd,J=8.0Hz,1.6Hz), 8.12(dd,1H,J=4.8Hz,2.0Hz), 7.39-7.49(4H,m), 7.24-7.27(1H,m), 5.29(1H,d,J=3.6Hz), 3.30(1H,d, J=3.6Hz)
1H-NMR(CDCl3,TMS)δ(ppm): 9.00(1H,s), 8.71(1H,dd,J=8.0Hz,1.6Hz), 8.12(dd,1H,J=4.8Hz,2.0Hz), 7.39-7.49(4H,m), 7.24-7.27(1H,m), 5.29(1H,d,J=3.6Hz), 3.30(1H,d, J=3.6Hz)
To 10 ml of ethyleneglycoldimethylether, 0.72 g of
N-(2-chloro-pyridine-3-yl)-2-hydroxy-2-(4-chlorophenyl)acetam
ide, 1.57 g of 3,4-dimethoxyphenylboronic acid, 1.7 g of
tripotassium phosphate hydrate and 63 mg of {1,1'
-bis(diphenylphosphino)ferrocene}dichloropalladium(II)
methylenechloride complex were mixed, followed by stirring under
a nitrogen atmosphere at 80 °C for 3 hours. Thereafter, the reaction
mixture was cooled down to room temperature and then filtrated,
followed by concentrating the filtrate under reduced pressure.
The residue was subjected to a silica gel column chromatography
to obtain 0.54 g of
N-{2-(3,4-dimethoxyphenyl)pyridine-3-yl}-2-hydroxy-2-(4-chlor
ophenyl)acetamide (, which is referred to as the compound of the
present invention (I-2) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 8.69(1H,dd,J=8.4Hz,1.2Hz), 8.45(1H,s), 8.36(1H,dd,J=4.4Hz,1.6Hz), 7.24-7.33(5H,m), 7.01(1H,s), 6.82-6.83(2H,m), 5.03(1H,d,J=2.4Hz), 4.04(1H,s), 3.95(3H,s), 3.87(3H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 8.69(1H,dd,J=8.4Hz,1.2Hz), 8.45(1H,s), 8.36(1H,dd,J=4.4Hz,1.6Hz), 7.24-7.33(5H,m), 7.01(1H,s), 6.82-6.83(2H,m), 5.03(1H,d,J=2.4Hz), 4.04(1H,s), 3.95(3H,s), 3.87(3H,s)
To 10 ml of tetrahydrofuran, 0.34 g of
N-{2-(3,4-dimethoxyphenyl)pyridine-3-yl}-2-hydroxy-2-(4-chlor
ophenyl) acetamide and 0.24 ml of triethylamine were mixed and then
further mixed with 0.10 ml of methanesulfonyl chloride at about
0 °C, followed by stirring at room temperature for 2 hours.
Thereafter, the reaction mixture was added with water to be extracted
with ethylacetate. The organic layer was washed by 1 % hydrochloric
acid and water, and then dried by magnesium sulfate, followed by
concentration under reduced pressure to obtain
N-{2-(3,4-dimethoxyphenyl)pyridine-3-yl}-2-methanesulfonyloxy
-2-(4-chlorophenyl)acetamide (, which is referred to as the
compound of the present invention (1-3) hereinafter). This
N-{2-(3,4-dimethoxyphenyl)pyridine-3-yl}-2-methanesulfonyloxy
-2-(4-chlorophenyl) acetamide and 1.5 ml of 2-prapyn-1-ol were mixed,
followed by stirring at about 80 °C for 3 hours. Thereafter, the
reaction mixture was cooled down to room temperature and then added
with water, followed by extraction with ethylacetate. The organic
layer was successively washed by 3 % hydrochloric acid, aqueous
saturated sodium bicarbonate and aqueous saturated sodium chloride,
and then dried by magnesium sulfate, followed by concentration
under reduced pressure. The residue was subjected to a silica gel
column chromatography to obtain 123 mg of
N-{2-(3,4-dimethoxyphenyl)-pyridine-3-yl}-2-(2-propynyloxy)-2-(4-chlorophenyl)acetamide
(the compound of the present invention
(I-1)}.
To the mixture of 8 g of aluminum chloride and 80 ml of
dichloromethane, 7.85 g of ethyloxalyl chloride was added dropwise
at 0 °C, and further 4.60 g of toluene being added dropwise at the
same temperature, followed by stirring at room temperature for
1 hour. Thereafter, the reaction mixture was added to ice water
to be extracted by chloroform. The organic layer was washed twice
by aqueous saturated sodium chloride and then dried by magnesium
sulfate followed by concentration under reduced pressure to obtain
9.3 g of 4-methylphenylglyoxylic acid ethyl ester as a crude product.
1H-NMR(CDCl3,TMS)δ(ppm): 7.91(2H,d,J=8.2Hz), 7.31(2H,d,J=8.1Hz), 4.44(2H,q,J=7.1Hz), 2.44(3H,s), 1.42(2H,t,J=7.0Hz)
9.3 g of 4-methylphenylglyoxylic acid ethyl ester, 13 ml of aqueous 30 % sodium hydroxide and 15 ml of ethanol were mixed, followed by heating with reflux for 2 hours. Thereafter, the reaction mixture was cooled down to room temperature, and then the reaction mixture was acidified by addition of 5 % hydrochloric acid to be extracted by ethylacetate. The organic layer was washed twice by aqueous saturated sodium chloride and then dried by magnesium sulfate, followed by concentration under reduced pressure. The residue was washed by hexane, followed by drying to obtain 5.2 g of 4-methylphenylglyoxylic acid.
1H-NMR(CDCl3, TMS)δ(ppm): 8.25(2H,d,J=8.3Hz), 7.32(2H,d,J=8.0Hz), 4.28(1H,br), 2.45(3H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 7.91(2H,d,J=8.2Hz), 7.31(2H,d,J=8.1Hz), 4.44(2H,q,J=7.1Hz), 2.44(3H,s), 1.42(2H,t,J=7.0Hz)
9.3 g of 4-methylphenylglyoxylic acid ethyl ester, 13 ml of aqueous 30 % sodium hydroxide and 15 ml of ethanol were mixed, followed by heating with reflux for 2 hours. Thereafter, the reaction mixture was cooled down to room temperature, and then the reaction mixture was acidified by addition of 5 % hydrochloric acid to be extracted by ethylacetate. The organic layer was washed twice by aqueous saturated sodium chloride and then dried by magnesium sulfate, followed by concentration under reduced pressure. The residue was washed by hexane, followed by drying to obtain 5.2 g of 4-methylphenylglyoxylic acid.
1H-NMR(CDCl3, TMS)δ(ppm): 8.25(2H,d,J=8.3Hz), 7.32(2H,d,J=8.0Hz), 4.28(1H,br), 2.45(3H,s)
To 150 ml of toluene, 10.0 g of 4-methylphenylglyoxylic acid,
7.2 ml of thionyl chloride and 0.2 g of N,N-dimethylformamide were
mixed, followed by stirring at 80 °C for 1 hour. Thereafter, the
reaction mixture was cooled down to room temperature, and then
said reaction mixture was concentrated under reduced pressure to
obtain 12.1 g of 4-methylphenylglyoxyl chloride.
To the solution prepared by mixing 2.1 g of 3-amino-2-chloropyridine
and 2.5 ml of triethylamine to 50 ml of tetrahydrofuran, 3 g of
4-methylphenylglyoxyl chloride was mixed at the temperature range
of from 0 to 5 °C, followed by stirring at room temperature for
4 hours. Then the reaction mixture was added with water to be
extracted with ethylacetate.
The organic layer was successively washed by 5 % hydrochloric acid,
aqueous saturated sodium bicarbonate and aqueous saturated sodium
chloride and then dried by magnesium sulfate, followed by
concentration under reduced pressure. The residue was washed by
hexane to obtain 4.0 g of
N-(2-chloropyridine-3-yl)-2-oxo-2-(4-methylphenyl)acetamide.
1H-NMR(CDCl3,TMS) δ(ppm): 9.60(1H,s), 8.86(1H,dd,J=8.4, 1.6Hz), 8.35(2H,d,J=8.0Hz), 8.20(dd,1H,J=4.4,1.2Hz), 7.32-7.35(3H,m), 2.46(3H,s)
1H-NMR(CDCl3,TMS) δ(ppm): 9.60(1H,s), 8.86(1H,dd,J=8.4, 1.6Hz), 8.35(2H,d,J=8.0Hz), 8.20(dd,1H,J=4.4,1.2Hz), 7.32-7.35(3H,m), 2.46(3H,s)
To 10 ml of ethanol, 1.5 g of
N-(2-chloropyridine-3-yl)-2-oxo-2-(4-methylphenyl)acetamide
was dissolved and then added with 62 mg of sodium borohydride at
0 °C, followed by stirring at room temperature for 3 hours.
Thereafter, the reaction mixture was added with aqueous saturated
ammonium chloride to be extracted by ethylacetate. The organic
layer was successively washed by aqueous saturated sodium
bicarbonate and aqueous saturated sodium chloride, and then dried
by magnesium sulfate, followed by concentration under reduced
pressure to obtain 285 mg of
N-(2-chloropyridine-3-yl)-2-hydroxy-2-(4-methylphenyl)acetami
de.
1H-NMR(CDCl3,TMS)δ(ppm): 8.93(1H,s), 8.73(1H,dd,J=8.4,1.6Hz), 8.11(dd,1H,J=4.4,1.6Hz), 7.39(2H,d,J=8.0Hz), 7.22-7.26(3H,m), 5.25(1H,d,J=2.0Hz), 3.18(1H,d, J=2.0Hz), 2.36(3H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 8.93(1H,s), 8.73(1H,dd,J=8.4,1.6Hz), 8.11(dd,1H,J=4.4,1.6Hz), 7.39(2H,d,J=8.0Hz), 7.22-7.26(3H,m), 5.25(1H,d,J=2.0Hz), 3.18(1H,d, J=2.0Hz), 2.36(3H,s)
To 20 ml of ethyleneglycoldimethylether, 1.3 g of
N-(2-chloropyridine-3-yl)-2-hydroxy-2-(4-methylphenyl)acetami
de, 1.0 g of 3, 4-dimethoxyphenylboronic acid, 3.0 g of tripotassium
phosphate hydrate and 0.12 g of {1,1'
-bis(diphenylphosphino)ferrocene}dichloropalladium(II)
methylenechloride complex were mixed, followed by stirring under
a nitrogen atmosphere at 80 °C for 3 hours. Thereafter, the reaction
mixture was cooled down to room temperature to be filtrated, followed
by concentrating the filtrate under reduced pressure. The residue
was subjected to a silica gel column chromatography to obtain 2.4
g of
N-{2-(3,4-dimethoxyphenyl)pyridine-3-yl}-2-hydroxy-2-(4-methy
lphenyl)acetamide (, which is referred to as the compound of the
present invention (I-4) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 8.73(1H,d,J=8.0Hz), 8.40-8.41(1H,m), 8.37(1H,s), 7.15-8.24(4H,m), 7.01(1H,d,J=1.2Hz), 6.88-6.90(1H,m), 6.84(1H,d,J=8.4Hz), 5.08(1H,d,J=2.8Hz), 3.96(3H,s), 3.88(3H,s), 3.32(1H,d,J=2.8Hz), 2.37(3H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 8.73(1H,d,J=8.0Hz), 8.40-8.41(1H,m), 8.37(1H,s), 7.15-8.24(4H,m), 7.01(1H,d,J=1.2Hz), 6.88-6.90(1H,m), 6.84(1H,d,J=8.4Hz), 5.08(1H,d,J=2.8Hz), 3.96(3H,s), 3.88(3H,s), 3.32(1H,d,J=2.8Hz), 2.37(3H,s)
To 10 ml of tetrahydrofuran, 0.63 g of
N-{2-(3,4-dimethoxyphenyl)pyridine-3-yl}-2-hydroxy-2-(4-methy
lphenyl) acetamide and 0.3 ml of triethylamine were dissolved and
then added with 0.14 ml of methanesulfonyl chloride at about 0 °C,
followed by stirring at room temperature for 30 minutes.
Thereafter, the reaction mixture was added with water to be extracted
by ethylacetate. The organic layer was washed by water and then
dried by anhydrous magnesium sulfate, followed by concentration
under reduced pressure to obtain
N-{2-(3,4-dimethoxyphenyl)pyridine-3-yl}-2-methanesulfonyloxy
-2-(4-methylphenyl)acetamide (, which is referred to as the
compound of the present invention (1-5) hereinafter). This
N-{2-(3,4-dimethoxyphenyl)pyridine-3-yl}-2-methanesulfonyloxy
-2-(4-methylphenyl)acetamide and 2.5 ml of 2-propyn-1-ol were mixed,
followed by stirring at around 80 °C for 1 hour. Thereafter, the
reaction mixture was cooled down to room temperature and then added
with water to be extracted by ethylacetate. The organic layer was
successively washed by water, aqueous saturated ammonium chloride
and aqueous saturated sodium chloride, and then dried by magnesium
sulfate, followed by concentration under reduced pressure. The
residue was subjected to a silica gel column chromatography to
obtain 397 mg of
N-{2-(3,4-dimethoxyphenyl)pyridine-3-yl}-2-propynyloxy-2-(4-m
ethylphenyl)acetamide (, which is referred to as the compound of
the present invention (I-6) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 9.00(1H,s), 8.73(1H,dd,J=8.0Hz,1.6Hz), 8.42(1H,dd,J=4.4Hz,1.6Hz), 7.00-7.31(8H,m),5.07(1H,s),3.91-4.17(8H,m),2.47(1H,t,J=2.0Hz), 2.34(3H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 9.00(1H,s), 8.73(1H,dd,J=8.0Hz,1.6Hz), 8.42(1H,dd,J=4.4Hz,1.6Hz), 7.00-7.31(8H,m),5.07(1H,s),3.91-4.17(8H,m),2.47(1H,t,J=2.0Hz), 2.34(3H,s)
The mixture of 2.00 g of
N-(2-chloropyridine-3-yl)-2-oxo-2-(4-chlorophenyl)acetamide,
20 ml of ethanol, 800 mg of pyridine and 1.13 g of methoxyamine
hydrochloric acid salt were stirred at room temperature for 2 hours.
Thereafter, the reaction mixture was concentrated under reduced
pressure. The residue obtained was added with water to be extracted
by ethylacetate; the extract was washed twice by 5 % hydrochloric
acid and aqueous saturated sodium chloride followed by drying with
magnesium sulfate and then the solvent being distilled off under
reduced pressure; and the residue was washed by n-hexane followed
by filtration and drying to obtain 1.95 g of
N-(2-chloropyridine-3-yl)-2-methoxyimino-2-(4-chlorophenyl)ac
etamide.
1H-NMR(CDCl3,TMS)δ(ppm): 8.8-8.9(2H,m), 8.19(1H,dd,J=1.7Hz,4.6Hz), 7.60-7.70(2H,m), 7.30-7.40(2H,m), 4.14(3H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 8.8-8.9(2H,m), 8.19(1H,dd,J=1.7Hz,4.6Hz), 7.60-7.70(2H,m), 7.30-7.40(2H,m), 4.14(3H,s)
To 10 ml of ethyleneglycoldimethylether, 0.5 g of
N-(2-chloropyridine-3-yl)-2-methoxyimino-2-(4-chlorophenyl)acetamide,
0.31 g of
3,4-dimethoxyphenylboronic acid, 0.65 g of tripotassium phosphate
hydrate and 25 mg of {1,1'
-bis(diphenylphosphino)ferrocene}dichloropalladium(II)
methylenechloride complex were mixed, followed by stirring under
a nitrogen atmosphere at 80 °C for 2 hours. Thereafter, the reaction
mixture was cooled down to room temperature to be filtrated, followed
by concentration of the filtrate under reduced pressure. The
concentrated residue was subjected to a silica gel column
chromatography to obtain 0.55 g of
N-{2-(3,4-dimethoxyphenyl)pyridine-3-yl}-2-methoxyimino-2-(4-chlorophenyl)acetamide
(, which is referred to as the compound
of the present invention (I-7) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 8.81(1H,dd,J=8.7Hz,2.0Hz), 8.47(1H,dd,J=4.9Hz,1.6Hz), 8.34(1H,s), 6.92-7.60(m,8H), 3.93(6H,s), 3.87(3H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 8.81(1H,dd,J=8.7Hz,2.0Hz), 8.47(1H,dd,J=4.9Hz,1.6Hz), 8.34(1H,s), 6.92-7.60(m,8H), 3.93(6H,s), 3.87(3H,s)
To 50 ml of ethyleneglycoldimethylether, 0.92 g of
2-chloro-3-nitropyridine, 0.80 g of 4-methoxyphenylboronic acid,
3.4 g of tripotassium phosphate hydrate, 130 mg of {1,1'
-bis(diphenylphosphino)ferrocene}dichloropalladium(II)
methylenechloride complex and 1.5 g of celite were added, followed
by stirring under a nitrogen atmosphere at 80 °C for 1.5 hours.
Thereafter, the reaction mixture was cooled down to room temperature
to be filtrated, followed by concentration of the filtrate under
reduced pressure. The residue was subj ected to a silica gel column
chromatography to obtain 0.76 g of
2-(4-methoxyphenyl)-3-nitropyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 3.86(3H,s), 6.98(2H,d,J=8.7Hz), 7.37(1H,dd,J=4.7Hz,8.0Hz), 7.53(2H,d,J=8.7Hz), 8.08(1H,dd,J=1.4Hz,8.0Hz), 8.81(1H,dd,J=1.4Hz,4.7Hz) 0.76 g of 4-(4-methoxyphenyl)-3-nitropyridine was dissolved to 100 ml of ethanol at room temperature and then added with 50 mg of 5 % platinum-carbon, followed by stirring under a hydrogen atmosphere for 4 hours. Thereafter, the reaction mixture was filtrated thruogh celite, followed by concentration of the filtrate under reduced pressure. The residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 0.45 g of 3-amino-2-(4-methoxyphenyl)pyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 3.81(2H,br), 3.85(3H,s), 6.97-7.04(4H,m), 7.61(2H,d,J=8.7Hz), 8.10(1H,t,J=2.9Hz)
0.36 g of 2-(4-chlorophenyl)-2-(2-propynyloxy)acetyl chroride was added dropwise to the mixture of 0.25 g of 3-amino-2-(4-methoxyphenyl) pyridine, 0.19 g of triethylamine and 20 ml of tetrahydrofuran, followed by stirring at room temperature for 2 hours. Thereafter, the reaction mixture was added with ethylacetate and then filtrateed to remove insolubles. After the filtrate was concentrated under reduced pressure, the residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 0.55 g of N-(2-(4-methoxyphenyl)pyridine-3-yl)-2-(2-propynyloxy)-2-(4-c hlorophenyl) acetamide (, which is referred to as the compound of the present invention (I-8) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 2.49(1H,t,J=1.6Hz), 3.89(3H,s), 3.99(1H,dd,J=2.4Hz,15.8Hz), 4.18(1H,dd,J=2.4Hz,15.8Hz), 5.07(1H,s), 7.06(2H,d,J=8.7Hz), 7.21-7.26(1H,m), 7.30-7.37(4H,m), 7.54(2H,d,J=8.7Hz), 8.42(1H,dd,J=1.6Hz,4.7Hz), 8.64(1H,dd,J=1.6Hz,8.3Hz), 8.52(1H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 3.86(3H,s), 6.98(2H,d,J=8.7Hz), 7.37(1H,dd,J=4.7Hz,8.0Hz), 7.53(2H,d,J=8.7Hz), 8.08(1H,dd,J=1.4Hz,8.0Hz), 8.81(1H,dd,J=1.4Hz,4.7Hz) 0.76 g of 4-(4-methoxyphenyl)-3-nitropyridine was dissolved to 100 ml of ethanol at room temperature and then added with 50 mg of 5 % platinum-carbon, followed by stirring under a hydrogen atmosphere for 4 hours. Thereafter, the reaction mixture was filtrated thruogh celite, followed by concentration of the filtrate under reduced pressure. The residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 0.45 g of 3-amino-2-(4-methoxyphenyl)pyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 3.81(2H,br), 3.85(3H,s), 6.97-7.04(4H,m), 7.61(2H,d,J=8.7Hz), 8.10(1H,t,J=2.9Hz)
0.36 g of 2-(4-chlorophenyl)-2-(2-propynyloxy)acetyl chroride was added dropwise to the mixture of 0.25 g of 3-amino-2-(4-methoxyphenyl) pyridine, 0.19 g of triethylamine and 20 ml of tetrahydrofuran, followed by stirring at room temperature for 2 hours. Thereafter, the reaction mixture was added with ethylacetate and then filtrateed to remove insolubles. After the filtrate was concentrated under reduced pressure, the residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 0.55 g of N-(2-(4-methoxyphenyl)pyridine-3-yl)-2-(2-propynyloxy)-2-(4-c hlorophenyl) acetamide (, which is referred to as the compound of the present invention (I-8) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 2.49(1H,t,J=1.6Hz), 3.89(3H,s), 3.99(1H,dd,J=2.4Hz,15.8Hz), 4.18(1H,dd,J=2.4Hz,15.8Hz), 5.07(1H,s), 7.06(2H,d,J=8.7Hz), 7.21-7.26(1H,m), 7.30-7.37(4H,m), 7.54(2H,d,J=8.7Hz), 8.42(1H,dd,J=1.6Hz,4.7Hz), 8.64(1H,dd,J=1.6Hz,8.3Hz), 8.52(1H,s)
To 100 ml of ethyleneglycoldimethylether, 6.0 g of
2-chloro-3-nitropyridine, 7.9 g of
2-methoxy-4-(4,4,5,5,-tetramethyl-1,3,2-dioxaborane-2-yl)phen
ol, 19.8 g of tripotassium phosphate hydrate and 780 mg of {1,1'
-bis(diphenylphosphino)ferrocene}dichloropalladium(II)
methylenechloride complex were added, followed by stirring under
a nitrogen atmosphere at 80°C for 3 hours. Thereafter, the reaction
mixture was cooled down to room temperature to be filtrated, followed
by concentration of the filtrate under reduced pressure. The
residue was subjected to a silica gel column chromatography to
obtain 6.38 g of 2-(4-hydroxy-3-methoxyphenyl)-3-nitropyridine.
1H-NMR(CDCl3, TMS)δ(ppm): 3.93(3H,s), 6.14(1H,s), 6.96(1H,d,J=7.9Hz), 7.05(1H,dd,J=2.0Hz,7.9Hz), 7.17(1H,d,J=2.0Hz), 7.37(1H,dd,J=4.7Hz,7.9Hz), 8.05(1H,dd,J=1.6Hz,7.9Hz), 8.80(1H,dd,J=1.6Hz,4.7Hz)
1H-NMR(CDCl3, TMS)δ(ppm): 3.93(3H,s), 6.14(1H,s), 6.96(1H,d,J=7.9Hz), 7.05(1H,dd,J=2.0Hz,7.9Hz), 7.17(1H,d,J=2.0Hz), 7.37(1H,dd,J=4.7Hz,7.9Hz), 8.05(1H,dd,J=1.6Hz,7.9Hz), 8.80(1H,dd,J=1.6Hz,4.7Hz)
To 50 ml of N,N-dimethylformamide, 1.50 g of
2-(4-hydroxy-3-methoxyphenyl)-3-nitropyridine, 1.0 g of ethyl
iodide and 0.90 g of potassium carbonate were added, followed by
stirring at room temperature for 4 hours. The reaction solution
was added with water to be extracted by ethylacetate. The organic
layer obtained was concentrated under reduced pressure, followed
by subjecting the residue obtained to a silica gel column
chromatography to obtain 0.90 g of
2-(4-ethoxy-3-methoxyphenyl)-3-nitropyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 1.49(3H,t,J=7.1Hz), 3.92(3H,s), 4.15(2H,q,J=7.1Hz), 6.91(1H,d,J=8.3Hz), 7.09(1H,dd,J=2.0Hz,8.3Hz), 7.18(1H,d,J=2.0Hz), 7.37(1H,dd,J=4.7Hz,7.9Hz), 8.05(1,9,dd,J=1.6Hz,7.9Hz), 8.81(1H,dd,J=1.6Hz,4.7Hz)
1H-NMR(CDCl3,TMS)δ(ppm): 1.49(3H,t,J=7.1Hz), 3.92(3H,s), 4.15(2H,q,J=7.1Hz), 6.91(1H,d,J=8.3Hz), 7.09(1H,dd,J=2.0Hz,8.3Hz), 7.18(1H,d,J=2.0Hz), 7.37(1H,dd,J=4.7Hz,7.9Hz), 8.05(1,9,dd,J=1.6Hz,7.9Hz), 8.81(1H,dd,J=1.6Hz,4.7Hz)
To 100 ml of ethanol, 0.90 g of
2-(4-ethoxy-3-methoxyphenyl)-3-nitropyridine and 50 mg of 5 %
platinum-carbon were added, followed by stirring under a hydrogen
atmosphere for 4 hours. Thereafter, the reaction mixture was
filtrated through celite, followed by concentration of the filtrate
under reduced pressure. The residue was subjected to a silica gel
column chromatography (eluent; hexane/ethylacetate=1/1) to obtain
0.72 g of 3-amino-2-(4-ethoxy-3-methoxyphenyl)pyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 1.48(3H,t,J=6.8Hz), 3.88(2H,s), 3.91(3H,s), 4.14(2H,q,J=6.8Hz), 6.94(1H,d,J=8.8Hz), 7.03(2H,d,J=2.8Hz), 7.19-7.25(2H,m), 8.10(1H,t,J=2.8Hz)
1H-NMR(CDCl3,TMS)δ(ppm): 1.48(3H,t,J=6.8Hz), 3.88(2H,s), 3.91(3H,s), 4.14(2H,q,J=6.8Hz), 6.94(1H,d,J=8.8Hz), 7.03(2H,d,J=2.8Hz), 7.19-7.25(2H,m), 8.10(1H,t,J=2.8Hz)
The mixture of 0.20 g of
3-amino-2-(4-ethoxy-3-methoxyphenyl)pyridine, 0.15 g of
triethylamine and 10 ml of tetrahydrofuran was added dropwise with
0.30 g of 2-(4-chlorophenyl)-2-(2-propynyloxy)acetyl chloride,
followed by stirring at room temperature for 2 hours. Thereafter,
the reaction mixture was added with ethylacetate and then filtrated
to remove insolubles. After the filtrate being concentrated under
reduced pressure, the residue was subjected to a silica gel column
chromatography (eluent; hexane/ethylacetate =1/1) to obtain 0.30
g of
N-(2-(4-ethoxy-3-methoxyphenyl)pyridine-3-yl)-2-(2-propynylox
y)-2-(4-chlorophenyl)acetamide (, which is referred to as the
compound of the present invention (I-9) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 1.52(3H,t,J=7.1Hz), 2.49(1H,t,J=2.4Hz), 3.94(3H,s), 3.97(1H,dd,J=2.4Hz,15.8Hz), 4.18(1H,dd,J=2.4Hz,15.8Hz), 4.19(2H,q,J=7.1Hz), 5.08(1H,s), 7.01(1H,d,J=7.9Hz), 7.11-7.15(2H,m), 7.24(1H,dd,J=4.7Hz,7.9Hz), 7.31(2H,d,J=8.7Hz), 7.35(2H,d,J=8.7Hz), 8.42(1H,dd,J=1.6Hz,4.7Hz), 8.68(1H,dd,J=1.6Hz,7.9Hz), 8.96(1H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 1.52(3H,t,J=7.1Hz), 2.49(1H,t,J=2.4Hz), 3.94(3H,s), 3.97(1H,dd,J=2.4Hz,15.8Hz), 4.18(1H,dd,J=2.4Hz,15.8Hz), 4.19(2H,q,J=7.1Hz), 5.08(1H,s), 7.01(1H,d,J=7.9Hz), 7.11-7.15(2H,m), 7.24(1H,dd,J=4.7Hz,7.9Hz), 7.31(2H,d,J=8.7Hz), 7.35(2H,d,J=8.7Hz), 8.42(1H,dd,J=1.6Hz,4.7Hz), 8.68(1H,dd,J=1.6Hz,7.9Hz), 8.96(1H,s)
To 100 ml of N,N-dimethylformamide, 3.0 g of
2-(4-hydroxy-3-methoxyphenyl)-3-nitropyridine, 1.5 g of
3-bromo-1-propyne and 1.7 g of potassium carbonate were added,
followed by stirring at room temperature for 4 hours. The reaction
solution was added with dilute hydrochloric acid to be extracted
by ethylacetate. The organic layer was concentrated under reduced
pressure, followed by subjecting the residue obtained to a silica
gel column chromatography to obtain 1.8 g of
2-(3-methoxy-4-(2-propynyloxy)phenyl)-3-nitropyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 2.54(1H,t,J=2.4Hz), 3.92(3H,s), 4.81(2H,d,J=2.4Hz), 7.07-7.13(2H,m), 7.20(1H,d,J=1.6Hz), 7.39(1H,dd,J=4.7Hz,8.3Hz), 8.07(1H,dd,J=1.6Hz,8.3Hz), 8.82(1H,dd,J=1.6Hz,4.7Hz)
1H-NMR(CDCl3,TMS)δ(ppm): 2.54(1H,t,J=2.4Hz), 3.92(3H,s), 4.81(2H,d,J=2.4Hz), 7.07-7.13(2H,m), 7.20(1H,d,J=1.6Hz), 7.39(1H,dd,J=4.7Hz,8.3Hz), 8.07(1H,dd,J=1.6Hz,8.3Hz), 8.82(1H,dd,J=1.6Hz,4.7Hz)
The mixture of 5 ml of acetic acid, 30 ml of water and 1.3
g of iron powder was heated to 75 °C and then added dropwise with
1.6 g of solution of
2-(3-methoxy-4-(2-propynyloxy)phenyl)-3-nitropyridine
dissolved in 10 ml of ethylacetate. After being heated with reflux
for 3 hours, the reaction solution was added with aqueous sodium
bicarbonate to be extracted by ethylacetate. The organic layer
was dried by magnesium sulfate followed by concentration under
reduced pressure; and then the residue was subjected to a silica
gel column chromatography to obtain 1.4 g of
3-amino-2-(3-methoxy-4-(2-propynyloxy)phenyl)pyridine.
1H-NMR(CDCl3,TMS)δ(ppm): 2.52(1H,t,J=2.4Hz), 3.89(2H,s), 3.91(3H,s), 4.80(2H,d,J=2.4Hz), 7.02-7.05(2H,m), 7.10(1H,d,J=8.8Hz), 7.22-7.26(2H,m), 8.10(1H,ddd,J=0.4Hz,2.4Hz,3.6Hz)
0.25 g of 2-(4-chlorophenyl)-2-(2-propynyloxy)acetyl chloride was added dropwise to the mixture of 0.20 g of 3-amino-2-(3-methoxy-4-(2-propynyloxy)phenyl)pyridine, 0.15 g of triethylamine and 10 ml of tetrahydrofuran, followed by stirring at room temperature for 2 hours. Thereafter, the reaction mixture was added with ethylacetate and then filtrated to remove insolubles. After the filtrate was concentrated under reduced pressure, the concentrated residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 0.30 g of N-(2-(3-methoxy-4-(2-propynyloxy)phenyl)pyridine-3-yl)-2-(2-p ropynyloxy)-2-(4-chlorophenyl)acetamide (, which is referred to as the compound of the present invention (1-10) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 2.51(1H,t,J=2.4Hz), 2.55(1H,t,J=2.4Hz), 3.94(3H,s), 3.97(1H,dd,J=2.4Hz,16.2Hz), 4.18(1H,dd,J=2.4Hz,16.2Hz), 4.86(2H,d,J=2.4Hz), 5.08(1H,s), 7.12-7.20(3H,m), 7.25(1H,dd,J=4.7Hz,7.9Hz), 7.31(2H,d,J=8.3Hz), 7.35(2H,d,J=8.3Hz), 8.42(1H,dd,J=1.6Hz,4.7Hz), 8.68(1H,dd,J=1.6Hz,7.9Hz), 8.95(1H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 2.52(1H,t,J=2.4Hz), 3.89(2H,s), 3.91(3H,s), 4.80(2H,d,J=2.4Hz), 7.02-7.05(2H,m), 7.10(1H,d,J=8.8Hz), 7.22-7.26(2H,m), 8.10(1H,ddd,J=0.4Hz,2.4Hz,3.6Hz)
0.25 g of 2-(4-chlorophenyl)-2-(2-propynyloxy)acetyl chloride was added dropwise to the mixture of 0.20 g of 3-amino-2-(3-methoxy-4-(2-propynyloxy)phenyl)pyridine, 0.15 g of triethylamine and 10 ml of tetrahydrofuran, followed by stirring at room temperature for 2 hours. Thereafter, the reaction mixture was added with ethylacetate and then filtrated to remove insolubles. After the filtrate was concentrated under reduced pressure, the concentrated residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =1/1) to obtain 0.30 g of N-(2-(3-methoxy-4-(2-propynyloxy)phenyl)pyridine-3-yl)-2-(2-p ropynyloxy)-2-(4-chlorophenyl)acetamide (, which is referred to as the compound of the present invention (1-10) hereinafter).
1H-NMR(CDCl3,TMS)δ(ppm): 2.51(1H,t,J=2.4Hz), 2.55(1H,t,J=2.4Hz), 3.94(3H,s), 3.97(1H,dd,J=2.4Hz,16.2Hz), 4.18(1H,dd,J=2.4Hz,16.2Hz), 4.86(2H,d,J=2.4Hz), 5.08(1H,s), 7.12-7.20(3H,m), 7.25(1H,dd,J=4.7Hz,7.9Hz), 7.31(2H,d,J=8.3Hz), 7.35(2H,d,J=8.3Hz), 8.42(1H,dd,J=1.6Hz,4.7Hz), 8.68(1H,dd,J=1.6Hz,7.9Hz), 8.95(1H,s)
10 g of 4-chlorophenylglyoxylic acid methyl ester was
dissolved to 100 ml of acetonitrile and then added with 40 g of
triphenylphosphine and 23 g of carbon tetrachloride, followed by
stirring at room temperature for 4 hours. The reaction solution
was concentrated to subject the residue to a silica gel column
chromatography (eluent; hexane/ethylacetate =10/1) to obtain 13.7
g of 2-(chlorophenyl)-3,3-dichloroacrylic acid methyl ester.
1 H-NMR(CDCl3,TMS)δ(ppm): 3.79(3H,s), 7.30(2H,d,J=8.3Hz), 7.37(2H,d,J=8.3Hz)
13.5 g of 2-(chlorophenyl)-3,3-dichloroacrylic acid methyl ester was dissolved to 130 ml of methanol and then added dropwise with aqueous potassium hydroxide (4.0 g of potassium hydroxide, 70 ml of water). After being stirred at room temperature for 8 hours, the reaction solution was semi-concentrated, followed by addition of dilute hydrochloric acid to be extracted by ethylacetate. The organic layer was dried by magnesium sulfate, followed by concentration under reduced pressure. The crystal obtained was washed by hexane to obtain 9.0 g of 2-(chlorophenyl)-3,3-dichloroacrylic acid.
1H-NMR(CDCl3,TMS)δ(ppm): 7.28(2H,dd,J=1.6Hz,8.3Hz), 7.38(2H,dd,J=1.6Hz,8.3Hz), 10.25(1H,br)
0.63 g of 2-(chlorophenyl)-3,3-dichloroacrylic acid and 0.36 g of thionyl chloride were added to 10 ml of toluene, followed by being heated under stirring for 2 hours. The reaction solution was concentrated under reduced pressure to obtain a crude 2-(chlorophenyl)-3,3-dichloroacryl chloride. The crude 2-(chlorophenyl)-3,3-dichloroacryl chloride obtained was added dropwise to 10 ml of tetrahydrofuran solution containing of 0.50 g of triethylamine and 0.30 g of 3-amino-2-(3,4-dimethoxyphenyl)pyridine, followed by stirring at room temperature for 3 hours; and then the reaction solution was added with ethylacetate and then filtrated to remove insolubles. The filtrate was concentrate under reduced pressure, followed by subjecting the residue to a silica gel column chromatography to obtain 60 mg of N-(2-(3,4-dimethoxyphenyl)-pyridine-3-yl)-2-(chlorophenyl)-3, 3-dichloroacrylamide.
1H-NMR(CDCl3,TMS)δ(ppm): 3.83(3H,s), 3.95(3H,s), 6.65-6.70(2H,m), 6.93(1H,s), 7.23-7.31(3H,m), 7.37(2H,d,J=7.6Hz), 7.49(1H,s), 8.41(1H,d,J=4.8Hz), 8.72(1H,d,J=8.4Hz)
1 H-NMR(CDCl3,TMS)δ(ppm): 3.79(3H,s), 7.30(2H,d,J=8.3Hz), 7.37(2H,d,J=8.3Hz)
13.5 g of 2-(chlorophenyl)-3,3-dichloroacrylic acid methyl ester was dissolved to 130 ml of methanol and then added dropwise with aqueous potassium hydroxide (4.0 g of potassium hydroxide, 70 ml of water). After being stirred at room temperature for 8 hours, the reaction solution was semi-concentrated, followed by addition of dilute hydrochloric acid to be extracted by ethylacetate. The organic layer was dried by magnesium sulfate, followed by concentration under reduced pressure. The crystal obtained was washed by hexane to obtain 9.0 g of 2-(chlorophenyl)-3,3-dichloroacrylic acid.
1H-NMR(CDCl3,TMS)δ(ppm): 7.28(2H,dd,J=1.6Hz,8.3Hz), 7.38(2H,dd,J=1.6Hz,8.3Hz), 10.25(1H,br)
0.63 g of 2-(chlorophenyl)-3,3-dichloroacrylic acid and 0.36 g of thionyl chloride were added to 10 ml of toluene, followed by being heated under stirring for 2 hours. The reaction solution was concentrated under reduced pressure to obtain a crude 2-(chlorophenyl)-3,3-dichloroacryl chloride. The crude 2-(chlorophenyl)-3,3-dichloroacryl chloride obtained was added dropwise to 10 ml of tetrahydrofuran solution containing of 0.50 g of triethylamine and 0.30 g of 3-amino-2-(3,4-dimethoxyphenyl)pyridine, followed by stirring at room temperature for 3 hours; and then the reaction solution was added with ethylacetate and then filtrated to remove insolubles. The filtrate was concentrate under reduced pressure, followed by subjecting the residue to a silica gel column chromatography to obtain 60 mg of N-(2-(3,4-dimethoxyphenyl)-pyridine-3-yl)-2-(chlorophenyl)-3, 3-dichloroacrylamide.
1H-NMR(CDCl3,TMS)δ(ppm): 3.83(3H,s), 3.95(3H,s), 6.65-6.70(2H,m), 6.93(1H,s), 7.23-7.31(3H,m), 7.37(2H,d,J=7.6Hz), 7.49(1H,s), 8.41(1H,d,J=4.8Hz), 8.72(1H,d,J=8.4Hz)
To 10 ml of toluene, 0.19 g of
-2-(4-chlorophenyl)-2-methoxyacetic acid and 0.14 g of thionyl
chloride were added, followed by being heated under stirring for
2 hours. The reaction solution was concentrated under reduced
pressure to obtain a crude 2-(chlorophenyl)-2-methoxyacetyl
chloride. The crude 2-(chlorophenyl)-2-methoxyacetyl chloride
obtained was added dropwise at 0 °C to 10 ml of tetrahydrofuran
solution containing 0.11 g of triethylamine and 0.22 g of
3-amino-2-(3,4-dimethoxyphenyl)pyridine. After being stirred at
room temperature for 3 hours, the reaction solution was concentrated
under reduced pressure, followed by subjecting the residue to a
silica gel column chromatography to obtain 127 mg of
N-(2-(3,4-dimethoxyphenyl)-pyridine-3-yl)-2-(4-chlorophenyl)-2-methoxyacetamide.
1H-NMR(CDCl3,TMS)δ(ppm): 3.31(3H,s), 3.95(3H,s), 3.98(3H,s), 4.67(1H,s), 7.00(1H,d,J=8.0Hz), 7.10-7.16(2H,m), 7.24(1H,dd,J=4.8Hz,8.4Hz), 7.30(2H,d,J=8.4Hz), 7.35(2H,d,J=8.4Hz), 8.42(1H,dd,J=1.6Hz,4.8Hz), 8.67(1H,dd,J=1.6Hz,8.4Hz), 8.95(1H,s)
1H-NMR(CDCl3,TMS)δ(ppm): 3.31(3H,s), 3.95(3H,s), 3.98(3H,s), 4.67(1H,s), 7.00(1H,d,J=8.0Hz), 7.10-7.16(2H,m), 7.24(1H,dd,J=4.8Hz,8.4Hz), 7.30(2H,d,J=8.4Hz), 7.35(2H,d,J=8.4Hz), 8.42(1H,dd,J=1.6Hz,4.8Hz), 8.67(1H,dd,J=1.6Hz,8.4Hz), 8.95(1H,s)
Next, the illustrated below is a referential production
example producing a production intermediate for the compound of
the present invention.
80.2 g of 4-chlorophenylglyoxylic acid methyl ester was
dissolved to 500 ml of methanol and then added with 3.8 g of sodium
borohydride at the temperature range of from 0 to 5 °C, followed
by stirring at room temperature for 2 hours. Thereafter, the
reaction mixture was concentrated under reduced pressure, followed
by addition of water to the residue to be extracted by ethylacetate.
The organic layer was concentrated under reduced pressure, followed
by subjecting the concentrated residue to a silica gel column
chromatography (eluent; hexane/ethylacetate = 5/1 to 2/1) to obtain
62.4 g of 2-hydroxy-2-(4-chlorophenyl)acetic acid methyl ester.
1H-NMR(CDCl3,TMS)δ(ppm): 3.51(1H,d,J=5.3Hz), 3.76(3H,S), 5.15(1H,d,J=5.3Hz), 7.31-7.38(4H,m)
1H-NMR(CDCl3,TMS)δ(ppm): 3.51(1H,d,J=5.3Hz), 3.76(3H,S), 5.15(1H,d,J=5.3Hz), 7.31-7.38(4H,m)
To 200 ml of tetrahydrofuran, 62.4 g of
2-hydroxy-2-(4-chlorophenyl)acetic acid methyl ester and 40.8 g
of triethylamine were dissolved and then added with 42.8 g of
methanesulfonyl chloride at 0 °C, followed by stirring at room
temperature for 3 hours. Thereafter, the reaction mixture was
concentrated under reduced pressure, followed by addition of
ethylacetate to the residue and then filtrated to remove solid
material. After the filtrate being concentrated under reduced
pressure, the residue was subjected to a silica gel column
chromatography (eluent; hexane/ethylacetate =3/1) to obtain 75.6
g of 2-methanesulfonyloxy-2-(4-chlorophenyl)acetic acid methyl
ester.
1H-NMR(CDCl3,TMS)δ(ppm): 3.12 (3H,s), 3.78 (3H,s), 5.92(1H,s), 7.36-7.43(4H,m)
70 g of 2-methanesulfonyloxy-2-(4-chlorophenyl) acetic acid methyl ester was mixed with 70 g of 2-propynylalcohol, followed by stirring at 80°C for 1.5 hours. Thereafter, the reaction mixture was added with toluene followed by concentration under reduced pressure. The concentrated residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =10/1) to obtain 64.6 g of a mixture of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid methyl ester and 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid (2-propynyl). (2-propynyloxy)-2-(4-chlorophenyl)acetic acid (2-propynyl)
1H-NMR(CDCl3,TMS)δ(ppm): 2.47(1H,t,J=2.4Hz), 2.51(1H,t,J=2.4Hz), 4.18(2H,dd,J=2.4Hz,16.2Hz), 4.31(2H,dd,J=2.4Hz,16.2Hz), 4.67(2H,dd,J=2.4Hz,15.4Hz), 4.76(2H,dd,J=2.4Hz,15.4Hz), 5.23(1H,s), 7.33-7.42(4H,m) 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid methyl ester
1H-NMR(CDCl3,TMS)δ(ppm): 2.50(1H,t,J=2.4Hz), 3.12(3H,s), 4.16(2H,dd,J=2.4Hz,16.2Hz), 4.30(2H,dd,J=2.4Hz,16.2Hz), 5.19(1H,s), 7.33-7.42(4H,m)
64.6 g of the mixture of (2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid methyl ester and 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid (2-propynyl), which mentioned above, were dissolved to 800 ml of tetrahydrofuran and then added dropwise at 0 °C with aqueous lithium hydroxide (a mixture of 6.74 g of lithium hydroxide and 280 ml of water). After being stirred in the range of from 0 °C to room temperature for 3 hours, the reaction solution was added with dilute hydrochloric acid to be extracted by ethylacetate. The organic layer was dried by anhydrous magnesium sulfate, followed by concentration under reduced pressure. The crystal produced was washed by hexane to obtain 43.4 g of 2-(2-propynyloxy)-2-(4-chlorophenyl) acetic acid (Intermediate 5-003).
1H-NMR(CDCl3,TMS)δ(ppm): 2.51(1H,t,J=2.4Hz), 4.15(1H,dd,J=2.4Hz,16.0Hz), 4.32(1H,dd,J=2.4Hz,16.0Hz), 7.33-7.44(4H,m), 8.70-9.50(1H,br)
4.7 g of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid and 3.0 g of thionyl chloride were dissolved to 50 ml of toluene, followed by stirring at 100 °C for 2 hours. The reaction solution was concentrated under reduced pressure to obtain 5.0 g of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid chloride.
1H-NMR(CDCl3,TMS)δ(ppm): 2.57(1H,t,J=2.0Hz), 4.28(1H,dd,J=2.0Hz,16.2Hz), 4.36(1H,dd,J=2.0Hz,16.2Hz), 5.39(1H,s), 7.37-7.44(4H,m)
1H-NMR(CDCl3,TMS)δ(ppm): 3.12 (3H,s), 3.78 (3H,s), 5.92(1H,s), 7.36-7.43(4H,m)
70 g of 2-methanesulfonyloxy-2-(4-chlorophenyl) acetic acid methyl ester was mixed with 70 g of 2-propynylalcohol, followed by stirring at 80°C for 1.5 hours. Thereafter, the reaction mixture was added with toluene followed by concentration under reduced pressure. The concentrated residue was subjected to a silica gel column chromatography (eluent; hexane/ethylacetate =10/1) to obtain 64.6 g of a mixture of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid methyl ester and 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid (2-propynyl). (2-propynyloxy)-2-(4-chlorophenyl)acetic acid (2-propynyl)
1H-NMR(CDCl3,TMS)δ(ppm): 2.47(1H,t,J=2.4Hz), 2.51(1H,t,J=2.4Hz), 4.18(2H,dd,J=2.4Hz,16.2Hz), 4.31(2H,dd,J=2.4Hz,16.2Hz), 4.67(2H,dd,J=2.4Hz,15.4Hz), 4.76(2H,dd,J=2.4Hz,15.4Hz), 5.23(1H,s), 7.33-7.42(4H,m) 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid methyl ester
1H-NMR(CDCl3,TMS)δ(ppm): 2.50(1H,t,J=2.4Hz), 3.12(3H,s), 4.16(2H,dd,J=2.4Hz,16.2Hz), 4.30(2H,dd,J=2.4Hz,16.2Hz), 5.19(1H,s), 7.33-7.42(4H,m)
64.6 g of the mixture of (2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid methyl ester and 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid (2-propynyl), which mentioned above, were dissolved to 800 ml of tetrahydrofuran and then added dropwise at 0 °C with aqueous lithium hydroxide (a mixture of 6.74 g of lithium hydroxide and 280 ml of water). After being stirred in the range of from 0 °C to room temperature for 3 hours, the reaction solution was added with dilute hydrochloric acid to be extracted by ethylacetate. The organic layer was dried by anhydrous magnesium sulfate, followed by concentration under reduced pressure. The crystal produced was washed by hexane to obtain 43.4 g of 2-(2-propynyloxy)-2-(4-chlorophenyl) acetic acid (Intermediate 5-003).
1H-NMR(CDCl3,TMS)δ(ppm): 2.51(1H,t,J=2.4Hz), 4.15(1H,dd,J=2.4Hz,16.0Hz), 4.32(1H,dd,J=2.4Hz,16.0Hz), 7.33-7.44(4H,m), 8.70-9.50(1H,br)
4.7 g of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid and 3.0 g of thionyl chloride were dissolved to 50 ml of toluene, followed by stirring at 100 °C for 2 hours. The reaction solution was concentrated under reduced pressure to obtain 5.0 g of 2-(2-propynyloxy)-2-(4-chlorophenyl)acetic acid chloride.
1H-NMR(CDCl3,TMS)δ(ppm): 2.57(1H,t,J=2.0Hz), 4.28(1H,dd,J=2.0Hz,16.2Hz), 4.36(1H,dd,J=2.0Hz,16.2Hz), 5.39(1H,s), 7.37-7.44(4H,m)
Next formulation examples are shown. Parts represent parts
by weight.
Fifty parts of each of the compounds of the present invention
(I-1) to (I-12), (II-1), (III-1) and (IV-1), 3 parts of calcium
ligninsulfonate, 2 parts of magnesium laurylsulfate and 45 parts
of synthetic hydrated silica are pulverized and mixed well to give
wettable powders of each compound.
Twentyparts of each of the compounds of the present invention
(I-1) to (I-12), (II-1), (III-1) and (IV-1) and 1.5 parts of sorbitan
trioleate aremixedwith 28.5 parts of an aqueous solution containing
2 parts of polyvinyl alcohol, and wet-pulverized finely. To the
obtained mixture, 40 parts of an aqueous solution containing 0.05
part of xanthan gum and 0.1 part of aluminium magnesium silicate
is added and further 10 parts of propylene glycol are added to
give a flowable of each compound.
Two parts of each of the compounds of the present invention
(I-1) to (I-12), (II-1), (III-1) and (IV-1), 88 parts of kaolin
clay and 10 parts of talc are pulverized and mixed well to give
dusts of each compound.
Five parts of each of the compounds of the present invention
(I-1) to (I-12), (II-1), (III-1) and (IV-1), 14 parts of
polyoxyethylenestyryl phenyl ether, 6 parts of calcium
dodecylbenzenesulfonate and 75 parts of xylene are mixed well to
give emulsifiable concentrates of each compound.
Two parts of each of the compounds of the present invention
(I-1) to (I-12), (II-1), (III-1) and (IV-1), 1 part of synthetic
hydrated silica, 2 parts of calcium ligninsulfonate, 30 parts of
bentonite and 65 parts of kaolin clay are pulverized and mixed
well, and water is added thereto and kneeded, granulated and dried
to give granules of each compound.
Ten parts of each of the compounds of the present invention
(I-1) to (1-12), (II-1), (III-1) and (IV-1), 35 parts of white
carbon containing 50% by weight of ammonium polyoxyethylenealkyl
ether sulfate and 55 parts of water are mixed and wet pulverized
finely to give a flowable of each compound.
Next, it is shown that the compound of the present invention
are useful for controlling plant diseases.
Additionally, the control effect was evaluated by visually
observing the area of a lesion on a sample plant in investigation
and comparing the area of a lesion on a non-treatment plant and
the area of a lesion on a treated plant with the compound of the
present invention.
Sand loam was compacted in a plasticpot, andatomato (variety:
Ponterosa) was seeded and grown in a green house for 20 days. The
compounds of the present invention (I-1), (I-2), (I-4), (1-6) to
(I-10), (I-12), (II-1), (III-1) and (IV-1) were formulated to
flowable according to Formulation Example 6, then, diluted with
water to provide given concentration of 500ppm, and these diluted
solutions were sprayed onto stems and leaves so as to give sufficient
adhesion on the surface of the tomato leaves. After spraying, the
liquid on the stem was air-dried, and a suspension of zoosporangiua
of Phytophthora infestans (about 10,000 zoosporangiua were
contained in 1ml of the suspension) was inoculated by spraying.
The amount of the sprayed suspension was about 2 ml for one plent.
After inoculation, the plant was first grown for one day at 23°C
under 90 % or more humidity, then further grown for 4 days in the
green house, which was 24°C in daytime and 20°C in night-time.
Then, the areas of a lesion of the plants were obserbed.
The lesion areas on the plants treated with the compounds of the
present invention (I-1), (I-2), (I-4), (1-6) to (I-10), (I-12),
(II-1), (III-1) and (IV-1) were not more than 10% of the lesion
area on a non-treatment plant.
Sand loam was compacted in a plasticpot, andatomato (variety:
Ponterosa) was seeded and grown in a green house for 20 days. The
compounds of the present invention (I-11) was formulatedto flowable
according to Formulation Example 6, then, diluted with water to
provide given concentration of 200ppm, and this diluted solution
was sprayed onto stems and leaves so as to give sufficient adhesion
on the surface of the tomato leaves. After spraying, the liquid
on the stem was air-dried, and a suspension of zoosporangiua of
Phytophthora infestans (about 10,000 zoosporangiua were contained
in 1ml of the suspension) was inoculated by spraying. The amount
of the sprayed suspension was about 2 ml for one plent. After
inoculation, the plant was first grown for one day at 23°C under
90 % or more humidity, then further grown for 4 days in the green
house, which was 24°C in daytime and 20°C in night-time.
Then, the areas of a lesion of the plants were obserbed.
The lesion areas on the plants treated with the compounds of the
present invention (I-11) was not more than 10% of the lesion area
on a non-treatment plant.
Sand loam was compacted in a plastic pot, and a grape (variety:
Berry A) was seeded and grown in a green house for 40 days. The
compounds of the present invention (I-1), (I-2), (I-6) to (I-12),
(II-1), (III-1) and (IV-1) were formulated to flowable according
to Formulation Example 6, then, diluted with water to provide given
concentration of 200ppm, and these diluted solutions were sprayed
onto stems and leaves so as to give sufficient adhesion on the
surface of grape leaves. After spraying, the liquid on the stem
was air-dried, and a suspension of zoosporangiua of Plasmopara
viticola (about 10,000 zoosporangiua were contained in 1ml of the
suspension) was inoculated by spraying. The amount of the sprayed
suspension was about 2 ml for one plant. After inoculation, the
plant was first grown for one day at 23°C under 90 % or more humidity,
then further grown for 6 days in the green house, which was 24°C
in daytime and 20°C in night-time.
Then, the areas of a lesion of the plants were obserbed.
The lesion areas on the plants treated with the present compound
(I-1), (I-2), (I-6) to (I-12), (II-1), (III-1) and (IV-1) were
not more than 10% of the lesion area on a non-treatment plant.
Sand loam was compacted in a plasticpot, and a grape (variety:
Berry A) was seeded and grown in a green house for 40 days. The
compounds of the present invention (I-4) was formulated to flowable
according to Formulation Example 6, then, diluted with water to
provide given concentration of 200ppm, and this diluted solution
was sprayed onto stems and leaves so as to give sufficient adhesion
on the surface of grape leaves. After spraying, the liquid on the
stem was air-dried, and a suspension of zoosporangiua of Plasmopara
viticola (about 10,000 zoosporangiua were contained in 1ml of the
suspension) was inoculated by spraying. The amount of the sprayed
suspension was about 2 ml for one plant. After inoculation, the
plant was first grown for one day at 23°C under 90 % or more humidity,
then further grown for 6 days in the green house, which was 24°C
in daytime and 20°C in night-time.
Then, the areas of a lesion of the plants were obserbed.
The lesion areas on the plants treated with the present compound
(I-4) was not more than 10% of the lesion area on a non-treatment
plant.
The compound of the present invention has an excellent
controlling activity against plant diseases and is useful as an
active ingredient for the agent controlling plant diseases.
Claims (16)
- A phenylpyridine compound represented by the formula (1) : [, wherein, in the formula, R1, R2, R3, R4 and R5 independently represent a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 haloalkenyl group, a C2-C6 alkynyl group, a C2-C6 haloalkynyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C3-C6 alkenyloxy group, a C3-C6 haloalkenyloxy group, a C3-C6 alkynyloxy group, a C3-C6 haloalkynyloxy group, a C1-C6 alkylthio group, a C1-C6 haloalkylthio group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group or a cyano group; both of R2 and R3 may be combined to represent a trimethylene, a tetramethylene or -CH=CH-CH=CH-;
R6 represents a hydrogen atom or a C1-C3 alkyl group;
R7, R8 and R11 independently represent a hydrogen atom, a halogen atom or a C1-C3 alkyl group;
R9 and R10 independently represent a hydroxyl group, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 haloalkenyl group, a C2-C6 alkynyl group, a C2-C6 haloalkynyl group, a C2-C6 cyanoalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C3-C6 alkenyloxy group, a C3-C6 haloalkenyloxy group, a C3-C6 alkynyloxy group, a C3-C6 haloalkynyloxy group, a C2-C6 cyanoalkyloxy group, a C1-C6 alkylthio group, a C1-C6 haloalkylthio group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group, a nitro group, a benzyl group or a cyano group;
W1―W2=W3―W4 represents N―CR21=CR22―CR23, CR24―N=CR25―CR26, CR27 ―CR28=N―CR29 or CR30―CR31=CR32―N
{in which R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31 and R32 independently represent a hydrogen atom, a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group or a C1-C3 haloalkyl group};
X represents an oxygen atom or a sulfur atom;
Q represents a group illustrated by the following formulas of Q1 or Q2 {in which R14 represents a hydrogen atom or a C1-C3 alkyl group, R15 represents a hydrogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group, a C3-C6 cycloalkyl group, a (C1-C6 alkyl) carbonyl group, a (C1-C6 haloalkyl) carbonyl group, a (C1-C6 alkoxy)carbonyl group, a (C1-C6 haloalkoxy)carbonyl group, a (C3-C6 alkenyloxy) carbonyl group, a (C3-C6 haloalkenyloxy) carbonyl group, a (C3-C6 alkynyloxy)carbonyl group, a (C3-C6 haloalkynyloxy) carbonyl group or a C1-C3 alkylsulfonyl group,
Z1 represents an oxygen atom or a sulfur atom,
Z2 represents an oxygen atom, NOR16 (in which R16 represents a hydrogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group or a C3-C6 cycloalkyl group), CR17R18 (in which R17 represents a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C3-C6 alkenyloxy group, a C3-C6 haloalkenyloxy group, a C3-C6 alkynyloxy group, a C3-C6 haloalkynyloxy group or a C3-C6 cycloalkyloxy group and R18 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group) or NNR19R20 (in which R19 and R20 independently represent a hydrogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group or a C3-C6 cycloalkyl group)}]. - The phenylpyridine compound according to claim 1, wherein X is an oxygen atom.
- The phenylpyridine compound according to any one of claim 1 or 2, wherein R6 is a hydrogen atom.
- The phenylpyridine compound according to any one of claim 1 to 3, wherein Q is Q1, R14 is a hydrogen atom and Z1 is an oxygen atom.
- The phenylpyridine compound according to claim 4, wherein R15 is a hydrogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group or a C3-C6 cycloalkyl group.
- The phenylpyridine compound according to any one of claim 1 to 3, wherein Q is Q2 and Z2 is NOR16 (in which R16 is a hydrogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group or a C3-C6 cycloalkyl group).
- The phenylpyridine compound according to any one of claim 1 to 6, wherein R1, R4 and R5 are hydrogen atoms.
- The phenylpyridine compound according to any one of claim 1 to 6, wherein R1, R4 and R5 are hydrogen atoms and R2 is a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C3-C6 alkynyl group, a C1-C6 alkoxy group, a C3-C6 alkenyloxy group, a C3-C6 alkynyloxy group, a C1-C6 alkylthio group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group or a cyano group.
- The phenylpyridine compound according to any one of claim 1 to 6, wherein R1, R2, R4 and R5 are hydrogen atoms.
- The phenylpyridine compound according to any one of claim 1 to 9, wherein each of R9 and R10 is a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C3-C6 alkenyloxy group, a C3-C6 haloalkenyloxy group, a C3-C6 alkynyloxy group, a C3-C6 haloalkynyloxy group, a C2-C6 cyanoalkyloxy group or a C3-C6 cycloalkoxy group.
- The phenylpyridine compound according to any one of claim 1 to 9, wherein each of R9 and R10 is a C1-C4 alkoxy group.
- The phenylpyridine compound according to any one of claim 1 to 9, wherein R9 and R10 are methoxy groups.
- The phenylpyridine compound according to any one of claim 1 to 12, wherein R7, R8 and R11 are hydrogen atoms.
- The phenylpyridine compound according to any one of claim 1 to 13, wherein W1―W2=W3―W4 is N―CH=CH―CH, CH-N=CH-CH, CH-CH=N―CH or CH―CH=CH―N.
- A fungicidal composition comprising the phenylpyridine compound according to any one of claim 1 to 14 and a carrier.
- A method for controlling plant diseases comprising applying of the phenylpyridine compound according to any one of claim 1 to 14 for plants or soils.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002237942 | 2002-08-19 | ||
JP2002237942 | 2002-08-19 | ||
PCT/JP2003/010246 WO2004016594A1 (en) | 2002-08-19 | 2003-08-12 | Phenylpyridine compound and bactericidal composition containing the same |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1541557A1 true EP1541557A1 (en) | 2005-06-15 |
Family
ID=31884447
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP03788085A Withdrawn EP1541557A1 (en) | 2002-08-19 | 2003-08-12 | Phenylpyridine compound and bactericidal composition containing the same |
Country Status (4)
Country | Link |
---|---|
US (1) | US20060041144A1 (en) |
EP (1) | EP1541557A1 (en) |
AU (1) | AU2003255004A1 (en) |
WO (1) | WO2004016594A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007020381A3 (en) * | 2005-08-15 | 2007-05-03 | Syngenta Participations Ag | Process for the synthesis of mandipropamid and derivatives thereof |
WO2008073623A2 (en) * | 2006-11-02 | 2008-06-19 | Arete Therapeutics, Inc. | Soluble epoxide hydrolase inhibitors |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004080978A1 (en) * | 2003-03-11 | 2004-09-23 | Sumitomo Chemical Company, Limited | Amide compound and bactericidal composition comprising the same |
WO2004083193A1 (en) * | 2003-03-17 | 2004-09-30 | Sumitomo Chemical Company, Limited | Amide compound and bactericide composition containing the same |
CN111548269B (en) * | 2020-04-29 | 2023-10-27 | 兰州大学 | Preparation method of diaryl methane structural compound |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HUP9800087A3 (en) * | 1995-01-30 | 1999-03-29 | Bayer Ag | Alkoximino acetic acid amides, pesticidal compositions containing them, method for combating pests and process for the preparation of the compounds |
JP2001302605A (en) * | 2000-04-20 | 2001-10-31 | Sumitomo Chem Co Ltd | Biphenyl compound and its use |
DE50103550D1 (en) * | 2000-06-14 | 2004-10-14 | Basf Ag | USE OF PHENETHYLACRYLAMIDES, NEW PHENETHYLACRYLAMIDES AND PRODUCTION METHODS |
BRPI0112676B1 (en) * | 2000-07-24 | 2015-10-06 | Bayer Cropscience Ag | "Biphenylcarboxamides, their preparation process, and composition and process for combating unwanted microorganisms." |
-
2003
- 2003-08-12 US US10/522,588 patent/US20060041144A1/en not_active Abandoned
- 2003-08-12 WO PCT/JP2003/010246 patent/WO2004016594A1/en not_active Application Discontinuation
- 2003-08-12 EP EP03788085A patent/EP1541557A1/en not_active Withdrawn
- 2003-08-12 AU AU2003255004A patent/AU2003255004A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO2004016594A1 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007020381A3 (en) * | 2005-08-15 | 2007-05-03 | Syngenta Participations Ag | Process for the synthesis of mandipropamid and derivatives thereof |
AU2006281293B2 (en) * | 2005-08-15 | 2011-04-28 | Syngenta Participations Ag | Process for the synthesis of mandipropamid and derivatives thereof |
US8129560B2 (en) | 2005-08-15 | 2012-03-06 | Syngenta Crop Protection, Inc. | Process for the synthesis of mandipropamid and derivatives thereof |
TWI399363B (en) * | 2005-08-15 | 2013-06-21 | Syngenta Participations Ag | Process |
KR101305928B1 (en) * | 2005-08-15 | 2013-09-12 | 신젠타 파티서페이션즈 아게 | Process for the synthesis of mandipropamid and derivatives thereof |
WO2008073623A2 (en) * | 2006-11-02 | 2008-06-19 | Arete Therapeutics, Inc. | Soluble epoxide hydrolase inhibitors |
WO2008073623A3 (en) * | 2006-11-02 | 2009-04-09 | Arete Therapeutics Inc | Soluble epoxide hydrolase inhibitors |
Also Published As
Publication number | Publication date |
---|---|
AU2003255004A1 (en) | 2004-03-03 |
US20060041144A1 (en) | 2006-02-23 |
WO2004016594A1 (en) | 2004-02-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2004131392A (en) | Tetrazole compound and application thereof | |
JP2004131416A (en) | Tetrazole compound and plant disease controlling application thereof | |
US20060041144A1 (en) | Phenylpyridine compound and fungicidal compostion containing the same | |
EP2488496A1 (en) | Aminopropenoates as fungicides | |
JP4561245B2 (en) | Chromone compounds and uses thereof | |
JP2004137254A (en) | Phenyl pyridine compound and plant disease control method using the same | |
WO2004058724A1 (en) | Phenylpyrazole compound and method of controlling plant disease with the same | |
JP2005263639A (en) | Amide compound having 5-membered heterocyclic ring and use of the same | |
JP2012056945A (en) | Pyrazole-4-carboxamide derivative, method for producing the same, and horticultural fungicide having the pyrazole-4-carboxamide derivative as active ingredient | |
JP2005206571A (en) | N-(alfa-cyanobenzyl)amide and use thereof for controlling plant disease | |
JP2005047826A (en) | Phenylpyridine compound and its use | |
JP2004292432A (en) | Phenylpyrazine compound and use of the same | |
JP2006008545A (en) | alpha-(N-AMIDO)BENZYL NITRILE COMPOUND AND ITS APPLICATION | |
JP2005097251A (en) | Biphenyl compound and use thereof | |
JP2005350428A (en) | Six-membered heterocyclic ring-bearing amide compound and its application | |
JP2004307474A (en) | Phenylpyrazole compound and use of the same | |
JP2006169117A (en) | Amide compound and use thereof | |
JP2006001855A (en) | Amide compound and its application | |
JP2005041793A (en) | Naphthalene compound and use thereof | |
JP2006111608A (en) | Amide compound and use thereof | |
JP2004300140A (en) | Phenylisoxazole compound and use of the same | |
JP2006160671A (en) | Amide compound and its use | |
JP2006001854A (en) | N-(annelated benzyl)amide compound and its application to plant disease control | |
JP2005104954A (en) | Phenylpyrazole compound and its blight control use | |
US20060122064A1 (en) | Amides and method for plant diseases control with the same |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20050201 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR |
|
AX | Request for extension of the european patent |
Extension state: AL LT LV MK |
|
DAX | Request for extension of the european patent (deleted) | ||
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20080304 |